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  • 2000-2004  (78)
  • 1985-1989  (17,632)
  • 1840-1849
  • Polymer and Materials Science  (16,437)
  • Life Sciences (general)  (639)
  • pharmacokinetics  (634)
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Year
  • 101
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 36 (1989), S. 279-282 
    ISSN: 1432-1041
    Keywords: meptazinol ; rectal and oral administration ; pharmacokinetics ; first-pass metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of the centrally-acting analgesic meptazinol after oral and rectal administration to 15 healthy men. Each subject took a standard 200 mg tablet orally and Witepsol H12 suppositories containing 75, 100, and 150 mg of the drug in a cross-over design. Meptazinol plasma concentrations were measured by HPLC using fluorescence detection and the pharmacokinetics determined. The tmax values for the 100 mg and 150 mg suppositories (median =0.5 h) were statistically significantly shorter than for the tablet (median =1.13 h), suggesting that meptazinol was more rapidly absorbed via the rectal route. Despite substantial intersubject variation in Cmax the plasma concentrations after rectal dosage were higher than after oral administration. There was a statistically significant (p〈0.001) improvement in systemic availability for each of the suppository doses (mean approximately 15.5% compared with the oral tablet (mean approximately 4.5%).
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  • 102
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 36 (1989), S. 283-290 
    ISSN: 1432-1041
    Keywords: ibuprofen ; enantiomers ; stereoselective protein binding ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have developed a novel and reproducible method for determining the plasma protein binding of the two ibuprofen enantiomers in the presence of each other. The method involves the use of radiolabelled racemic ibuprofen, equilibrium dialysis, derivatization of the enantiomers to diastereomeric amides, high-performance liquid chromatography, and radiochemical analysis. We have determined the plasma protein binding of R(−)- and S(+)-ibuprofen in 6 healthy male volunteers after the oral administration of 800 mg racemic ibuprofen. The mean time-averaged percentage unbound of the R(−)-enantiomer, 0.419 was significantly less than that of the S(+)-enantiomer, 0.643, consistent with stereoselective plasma protein binding. The percentage unbound of each ibuprofen enantiomer was concentration-dependent over the therapeutic concentration range and was influenced by the presence of its optical antipode.
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  • 103
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 36 (1989), S. 323-324 
    ISSN: 1432-1041
    Keywords: theophylline ; fluoroquinolones ; drug interaction ; renal excretion ; pharmacokinetics ; clearance ratio
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
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  • 104
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 36 (1989), S. 407-409 
    ISSN: 1432-1041
    Keywords: oxazepam ; antipyrine ; glucuronidation ; drug metabolism ; very low calorie diet ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A very low calorie diet (Prodi) was administered to eleven otherwise healthy obese subjects for fourteen days. The daily intake of protein was 52.7 g and carbohydrate 25.7 g, corresponding to 360 kcal. The clearance of oxazepam and antipyrine was investigated before and after the diet period. Total oxazepam clearance was 1.04 ml·min−1·kg−1 and it decreased 0.88-fold after the diet. The mean clearance of unbound oxazepam was correspondingly reduced 0.88-fold. The elimination half-life increased to 1.22-times the control value, 7.9 h. No significant change was found in the volume of distribution or protein binding of oxazepam. Antipyrine clearance, estimated by the one-sample technique, was 52.4 and 51.8 ml·min−1, before and after the diet, respectively. It appears that a very low calorie diet with a sufficient protein and a very low carbohydrate content decreases the metabolism of oxazepam by glucuro-conjugation, whereas no effect was seen on the oxidative metabolism of antipyrine.
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  • 105
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 36 (1989), S. 467-471 
    ISSN: 1432-1041
    Keywords: nitrendipine ; renal failure ; pharmacokinetics ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and plasma protein binding of nitrendipine in patients with terminal renal failure have been compared with those in subjects with normal renal function. Kinetic parameters were calculated after a single 40 mg oral dose, an i.v. injection of 3 mg and after a 15 mg i.v. infusion of nitrendipine. Steady-state plasma levels were determined after 5 days of oral treatment with 20 mg b.d. Pharmacokinetic parameters and steady-state plasma levels in patients with renal failure did not differ from those in subjects with normal renal function. Nitrendipine was as highly bound to plasma proteins in patients with renal failure, as in subjects with normal renal function. The plasma protein did not differ between the two. The dosage of nitrendipine need not be modified for kinetic reasons in patients with renal failure.
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  • 106
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 36 (1989), S. 473-479 
    ISSN: 1432-1041
    Keywords: felodipine ; liver cirrhosis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nine patients (6 males, 3 females) with biopsy-proven liver cirrhosis participated in an open, cross-over, three centre study of the effect of impaired liver function on the pharmacokinetics of felodipine. Two of the nine patients had undergone porto-caval anastomosis. Each patient was given 0.75 mg i.v. and 10 mg p.o. on separate occasions. The results of this study have been compared with published data from younger subjects and elderly hypertensive patients. The mean peak plasma concentration normalized to a dose of 10 mg (Cmax 46 nmol/l) was twice as high in the cirrhotic patients as in the healthy subjects, but the bioavailability, f, (17.0%) was comparable. Subjects with a porto-caval shunt did not have higher f than the mean for the group. The volume of distribution at steady-state, Vss, was significantly lower than in the healthy subjects. Protein binding was significantly lower in the patients with cirrhosis: 99.46% compared to 99.64% in the healthy subjects. The weight-corrected clearance was 1/3 of the value in healthy subjects. No correlation between systemic availability and oral clearance was found, so it is proposed that felodipine is metabolized both in the liver and also in the gut wall. The results suggest that at least the starting dose should be reduced in patients with severe liver disease.
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  • 107
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 36 (1989), S. 481-485 
    ISSN: 1432-1041
    Keywords: felodipine ; theophylline ; absorption ; metabolism ; pharmacokinetics ; blood pressure ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten healthy male volunteers (mean age 26 years) received 200 mg theophylline aminopropanol orally 8-hourly for 4 days, followed by 5 mg felodipine 8-hourly for 6 days, and then the combination of oral felodipine and theophylline for a further 4 days. Plasma concentrations of theophylline and felodipine were determined, and theophylline and its metabolites in urine were also measured. Felodipine led to a reduction in the plasma AUC of theophylline of 18.3%. The metabolic and renal clearances of theophylline remained unchanged, but the total recovery of theophylline-derived products was significantly reduced during felodipine treatment. No change in felodipine pharmacokinetics was observed during simultaneous treatment with theophylline. Compared to theophylline treatment alone, the diastolic blood pressure was significantly reduced during felodipine treatment alone and in combination with theophylline. It is concluded that felodipine slightly but significantly lowered the plasma theophylline concentration by interfering with its absorption. The interaction in most instances would probably be of minor clinical consequence.
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  • 108
    ISSN: 1432-1041
    Keywords: terodiline ; elderly patients ; metabolites ; pharmacokinetics ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The elderly form an important target group for the treatment of urinary urge incontinence with drugs such as terodiline (Mictrol, Terolin). In order to evaluate its steady-state pharmacokinetics and tolerability in geriatric patients terodiline 12.5 mg b.d. was given to 28 hospitalized patients with urinary incontinence (mean age 85 years) for six weeks. The patients were monitored during the study and for 6 weeks afterwards, blood samples being taken at regular intervals. In addition to these multi-diseased and polymedicated patients, a small, homogenous group of healthy volunteers (mean age 40 years) was studied as a reference group, being given terodiline 12.5 mg b.d. for 2 weeks. Terodiline was generally well tolerated by the patients and no significant change in blood pressure or heart rate were found. One patient was withdrawn due to adverse effects. The mean terminal half-life of terodiline was 131 h and the clearance after oral administration (clearance/systemic availability) was 39 ml·min−1. The corresponding figures for the healthy volunteers were 57 h and 75 ml·min−1. The average steady-state serum concentration was 518 µg·l−1 in the geriatric patients and 238 µg·l−1 in the healthy volunteers. Steady-state was reached within 3 weeks in 20 of the 28 patients and within 5 weeks in 7 patients. In the geriatric patients the steady-state serum concentration of the main metabolite p-hydroxyterodiline, during the last three weeks on terodiline was 45 µg·l−1, 57 µg·l−1, and 45 µg·l−1, respectively, and a similar value was found in the healthy volunteers, 47 µg·l−1. The serum concentration of p-hydroxy-m-methoxyterodiline was 〈15 µg·l−1 both in the geriatric patients and in the healthy volunteers. Thus, terodiline 25 mg/day given to fragile elderly patients was well tolerated. It produced serum concentrations similar to those found after the standard dose of 37.5–50 mg given to younger, healthier patients.
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  • 109
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 36 (1989), S. 507-512 
    ISSN: 1432-1041
    Keywords: indomethacin ; diflunisal ; drug interaction ; glucuronidation ; pharmacokinetics ; faecal blood loss
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of treatment with diflunisal on the steady-state pharmacokinetics of indomethacin has been studied in 16 healthy volunteers. The steady-state plasma concentration and AUC of indomethacin were significantly increased two- to threefold during treatment with diflunisal and its total clearance and total volume of distribution were significantly decreased. The urinary recovery of total indomethacin (unchanged+glucuronides) was significantly lower during administration of diflunisal, whereas excretion of the indomethacin metabolites desmethylindomethacin and desbenzoylindomethacin and their glucuronides was not significantly altered. The results can be explained by selective inhibition of glucuronidation of unchanged indomethacin by diflunisal. The interaction appears clinically relevant as potentially dangerous side effects of indomethacin are related to its plasma concentration.
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  • 110
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 36 (1989), S. 513-516 
    ISSN: 1432-1041
    Keywords: dipyrone ; methylaminoantipyrine ; aging ; renal function ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of the dipyrone metabolite, 4-metylaminoantipyrine (MAA) was evaluated, following the administration of a single oral dose of dipyrone 1.0 g to 12 young (21–30 years) and 9 elderly (73–90 years) healthy volunteers. Maximal concentration, time to peak and absorption rate of MAA were similar for both groups. The elimination half-life was 2.6 (0.2) h for the young and 4.5 (0.5) h for the elderly subjects. Total clearance of MAA, corrected for lean body mass (LBM), was lower in the elderly than in the young 2.65 vs 3.97 ml·min−1·k−1 LBM. There was no differences between the groups in the apparent volume of distribution. A good correlation was found between the total body clearance of MAA and the creatinine clearance, which was also reduced in the elderly (r=0.61).
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  • 111
    ISSN: 1432-1041
    Keywords: salbutamol ; sublingual ; oral ; inhaled ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Administration of drugs by the sublingual route provides rapid systemic absorption and avoids first-pass metabolism. The purpose of the present study was to assess the pharmacokinetics, efficacy and adverse effects of standard salbutamol tablets given by this route to patients with asthma. Seven asthmatic patients were given either sublingual salbutamol tablet 2 mg (SL), swallowed tablet 2 mg (O), metered dose inhaler 200 µg (MDI) or placebo (PL), in a randomized single-blind cross-over design. Airways responses (FEV1, FVC, PEFR), finger tremor (Tr), heart rate (HR), plasma potassium (K) and plasma salbutamol were measured over a 6 h period following drug administration. There were highly significant changes in FEV1 with MDI, O and SL routes compared with PL, although the response to MDI was greater and more rapid than with O or SL. There were similar findings for FVC and PEFR responses. There were no adverse effects with MDI, whereas both 0 and SL produced significant tremor responses. There were no differences between O and SL for any of the pharmacodynamic parameters. In addition, pharmacokinetic profiles for O and SL were also similar apart from an initial delay in absorption with SL. There were however, no significant differences in any of the pharmacokinetic parameters, between O and SL. This suggests that buccal absorption of salbutamol was negligible, and that systemic absorption occurred after swallowing of the dissolved sublingual tablet. These results show that sublingual administration of salbutamol tablet has no clinical benefit over the oral route.
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  • 112
    Electronic Resource
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    Springer
    European journal of clinical pharmacology 37 (1989), S. 577-580 
    ISSN: 1432-1041
    Keywords: cefoperazone ; cirrhosis ; ascites ; pharmacokinetics ; ascitic fluid content
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of cefoperazone was studied in eleven cirrhotic patients with ascites after i.v. administration of a single dose of 15 mg·kg−1 (n=7) or after three doses of 15 mg·kg−1 given at 12 h intervals (n=4). The concentrations of cefoperazone in serum and ascitic fluid were determined by HPLC. The peak serum cefoperazone concentration after a single i.v. injection of 15 mg·kg−1 was 96.0 mg·l−1. The serum elimination half-life was longer (5.0 h) than in normal subjects. The penetration of cefoperazone into ascites was satisfactory (32.3% and 58.3% after single and repeated injections, respectively). Ascitic fluid concentrations of cefoperazone exceeded 5.4 mg·ml−1 from 0.5 to 6 h after the single i.v. injection, levels which are well above the MIC of most pathogens found in spontaneous bacterial peritonitis. Adjustment of the dose of cefoperazone in cases of severe hepatic insufficiency does not appear to be necessary provided that renal function is normal.
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  • 113
    Electronic Resource
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    Springer
    European journal of clinical pharmacology 37 (1989), S. 599-604 
    ISSN: 1432-1041
    Keywords: 4-methylpyrazole ; alcohol dehydrogenase inhibitor ; healthy volunteers ; pharmacokinetics ; saturable kinetics ; zero order elimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In order to evaluate the pharmacokinetic profile of the alcohol dehydrogenase inhibitor 4-methylpyrazole 4-MP, a placebo-controlled, double-blind, single-dose, randomized, sequential, ascending-dose “Phase-I study” was performed in healthy male volunteers at dose levels of 10 (n=4), 20 (n=4), 50 (n=4) and 100 mg·kg−1 (n=3). In the 10 and 20 mg·kg−1 group, the elimination of 4-MP from the plasma followed non-linear kinetics with mean rates of concentration decline of 3.66 and 5.05 µmol·1−1·h−1, respectively. In the two highest dose groups, the elimination also appeared to be non-linear although the patterns were not followed long enough to confirm this, The mean rates of concentration decline at the higher doses were significantly increased, up to 14.9 µmol·l−1·h−1 at 100 mg·kg−1. The average renal clearance of 4-MP was low, 0.016 ml·min−1·kg−1, and only 3% of the administered dose was excreted unchanged in the urine, indicating metabolism as the major route of elimination. Because of the apparently unusual kinetics following single dose treatment, thorough multiple dose studies need to be carried out to determine a safe dosage regimen for 4-MP.
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  • 114
    Electronic Resource
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    Springer
    European journal of clinical pharmacology 37 (1989), S. 231-233 
    ISSN: 1432-1041
    Keywords: antipyrine ; terbinafine ; drug metabolism ; drug interaction ; enzyme induction/inhibition ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The potential to inhibit drug metabolism of the new antifungal agent terbinafine has been studied using antipyrine (single oral dose of 10 mg/kg) as a probe drug. In a cross-over study in 8 healthy volunteers, antipyrine was administered prior to, during and after 8 days of oral terbinafine 125 mg b.d. Antipyrine, its major metabolites 4-hydroxyantipyrine (4-OH-AP), 3-hydroxymethylantipyrine (3-OH-CH3-AP) and norantipyrine (Nor-AP) were analyzed by specific HPLC assays in multiple plasma and urine samples. During all three parts of the study, the pharmacokinetics of antipyrine viz. t1/2 (11.7 h), total plasma (38.5 ml·h−1·kg−1) and renal clearance (1.6 ml·h−1·kg−1), and its clearance rates to metabolites (CLM), eg. CLM for 4-OH-AP (12.3 ml·h−1·kg−1), CLM for 3-OH-CH3-AP (4.2 ml·h−1·kg−1) and CLM for Nor-AP (6.7 ml·h−1·kg−1) did not differ from the control values. Thus, all the cytochrome P-450-dependent isozymes involved in the metabolism of antipyrine and many other drugs should not be affected by therapeutic doses of terbinafine.
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  • 115
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    European journal of clinical pharmacology 37 (1989), S. 245-248 
    ISSN: 1432-1041
    Keywords: breast milk ; zolpidem ; pharmacokinetics ; imidazopyridine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five, lactating, healthy white women were treated with a single 20 mg tablet of zolpidem 3–4 days after the delivery of a full term baby. The drug was administered at 20.00 h, 30 min after dinner, and milk samples were collected before and 3, 13 and 16 h. Venous blood 5 ml was taken before and 1.5, 3, 13, 16 h after zolpidem administration. The apparent elimination half life, estimated from plasma zolpidem concentrations was 2.6 h. The amount of zolpidem excreted in the milk at 3 h ranged between 0.76 and 3.88 µg, which represented 0.004 to 0.019% of the administered dose; no detectable (below 0.5 ng/ml) zolpidem was found in the milk at subsequent sampling times. The ratio of the zolpidem concentrations in breast milk and plasma at 3 h was 0.13. The apparent breast milk clearance of zolpidem, calculated from the ratio of the total amount of zolpidem excreted in milk to its AUC in plasma was 1.48 ml/h. The results show that the excretion of zolpidem in human milk is very low (below 0.02%) and that most of it takes place during the first 3 h following drug intake.
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  • 116
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    European journal of clinical pharmacology 37 (1989), S. 261-265 
    ISSN: 1432-1041
    Keywords: oflaxacin ; ascitic fluid ; cirrhosis ; drug penetration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma and ascitic fluid concentrations of ofloxacin were determined in 12 cirrhotic patients after a single dose and repeated 200 mg oral doses. The single dose kinetics were compared to those obtained in 12 healthy volunteers. Mean plasma elimination half-life was 11.6 h in cirrhotics and 7.0 h in controls. Mean total clearance was 2.3 times lower in patients than in controls, due to a significant decrease of renal clearance of the drug, unrelated to creatinine clearance. Mean apparent volume of distribution was 1.2 l/kg in patients and 1.8 l/kg in controls. Estimated by the ratio of AUC in peritoneal fluid and plasma, ascitic fluid penetration was 80% after the first oral dose. Ascitic fluid concentrations equaled corresponding plasma concentrations after 10 h, without pronounced accumulation of ofloxacin in ascites. We may conclude that, in cirrhotic patients with normal serum creatinine, a significant impairment of renal tubular handling of ofloxacin could be observed and led to a delayed elimination half-life of the drug. Because of its broad sprectrum of activity, low side-effect profile, and large ascitic fluid penetration after oral administration, ofloxacin appears to be a new therapeutic approach of severe infections in cirrhotic patients, in particular spontaneous bacterial peritonitis.
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  • 117
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    Springer
    European journal of clinical pharmacology 37 (1989), S. 267-272 
    ISSN: 1432-1041
    Keywords: midazolam ; pharmacokinetics ; children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A serum concentration profile study on midazolam in children was done. Fifty six children aged 3–10 years took part. The routes investigated were intravenous, intramuscular, rectal and oral at 0.15 mg·kg−1, and the oral at 0.45 mg·kg−1 and 1 mg·kg−1. Serum concentration levels for 5 h were studied using gas liquid chromatography. The volume of distribution, Vss, was 1.29 l·kg−1, the elimination half-life 1.17 h and the serum clearance 9.11 ml·kg−1·min−1. Peak serum concentrations for the intramuscular, rectal and oral routes were at 15 min, 30 min and 53 min respectively. Bioavailability was 87%, 18%, 27% respectively at a dose of 0.15 mg·kg−1. The oral route bioavailability halved to 15% at the two higher doses. Bioequivalence was present between the 0.15 mg·kg−1 intramuscular dose and the 0.45 mg·kg−1 oral dose from 45 to 120 min.
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  • 118
    ISSN: 1432-1041
    Keywords: nicotine ; transdermal delivery ; dose proportionality ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of nicotine delivered by a transdermal delivery system (TDS) was investigated in two separate studies, (A) a dose proportionality study and (B) a multiple dose study. In the dose range of 15–60 mg nicotine, the AUC and Cmax values were proportional to the dose. The levels achieved were in the same range as reported in smokers, following absorption from nicotine chewing gum. The TDS used in the present study produced sustained levels of nicotine for 24 h. No significant accumulation of nicotine was evident as a result of multiple dose administration using a 30-mg nicotine patch. Absorption of nicotine from the TDS was 80–90% and the rate of delivery was similar during both studies.
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  • 119
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    European journal of clinical pharmacology 37 (1989), S. 359-363 
    ISSN: 1432-1041
    Keywords: neuroleptics ; remoxipride ; pharmacokinetics ; urinary pH ; healthy volunteers ; overdose ; plasma prolactin ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of urinary pH on the plasma and urinary kinetics of remoxipride in man has been studied in an open crossover trial in ten healthy male volunteers. Ammonium chloride (urinary pH 5.2) and sodium hydrogen carbonate (urinary pH 7.8) were used as pretreatments on two occasions in randomized order. On each occasion remoxipride 50 mg solution was administered orally and plasma and urinary concentrations of the drug were determined by HPLC and plasma prolactin concentrations by RIA. Remoxipride was rapidly distributed in the body according to a one-compartment model. The mean plasma elimination half-life (t1/2) was 3.6 h in the ammonium chloride experiment and 6.2 h in the sodium hydrogen carbonate experiment. The mean plasma clearance of remoxipride was 141 and 89.9 ml·min−1 in the acidic and alkaline conditions, respectively, and the corresponding mean renal clearances were 58.5 ml·min−1 and 11.7 ml·min−1. The urinary excretion of remoxipride up to 72 h after drug administration was 43.1% and 12.3% following acidification and alkalinization, respectively. Remoxipride induced a similar rapid, transient elevation of plasma prolactin under both conditions. Thus, the urinary pH has a marked effect on the elimination kinetics of remoxipride. After an overdose, treatment with ammonium chloride might be valuable in hastening elimination of remoxipride from the body.
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  • 120
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    European journal of clinical pharmacology 36 (1989), S. 25-28 
    ISSN: 1432-1041
    Keywords: theophylline ; terbutaline ; asthma ; drug interaction ; hepatic metabolism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic mechanism of the theophylline-terbutaline interaction has been studied. Sustained release theophylline 200–400 mg b.d. was given with placebo or terbutaline 2.5 mg t.d.s. to six adult asthmatic patients. Terbutaline decreased the serum trough theophylline levels from 8.1 to 7.3 µg/ml, improved daily the clinical score from 1.51 to 1.26 and increased the peak expiratory flow rate from 316 to 370 l/min. In a single dose study following the chronic therapy, it was shown that there was no change in the peak theophylline concentration or in the timing of the peak, but the t1/2 was reduced from 9.0 to 7.5 h, and the systemic clearance was increased from 20.2 to 24.8 ml·h−1·kg−1. Thus, terbutaline reduced the serum theophylline concentration by increasing its systemic clearance.
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  • 121
    ISSN: 1432-1041
    Keywords: pirenzepine ; hepatic insufficiency ; hepato-renal insufficiency ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The steady-state intravenous pharmacokinetics of pirenzepine has been investigated in patients with chronic liver disease and others with combined chronic liver disease and renal sufficiency. The plasma clearance (CL) of Pirenzepine, steady-state plasma concentration Cmin(ss) and dominant half life t1/2γ were not significantly altered in the chronic liver disease group. In patients with renal and hepatic insufficiency, CL was reduced, t1/2γ was prolonged from 11.1 to 19.4 h and Cmin(ss) was elevated from 36 ng/ml to 66 ng/ml compared to healthy controls. Plasma concentrations remained in the therapeutic range and the dosage regimen was well tolerated. Adjustment of the dose of pirenzepine need be considered only in cases of severe impairment of both renal and hepatic elimination.
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  • 122
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    European journal of clinical pharmacology 36 (1989), S. 67-70 
    ISSN: 1432-1041
    Keywords: diltiazem ; propranolol ; metoprolol ; atenolol ; pharmacokinetics ; drug interaction ; beta-adrenoceptor blockade ; healthy volunteers ; pharmacodynamic effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic interaction between diltiazem and three β-adrenoceptor blockers propranolol, metoprolol and atenolol was investigated in healthy volunteers given diltiazem 30 mg or placebo t.d.s. for 3 days, followed by a single dose of propranolol 20 mg, metoprolol 40 mg or atenolol 50 mg. The AUCs of propranolol and metoprolol were significantly increased after diltiazem and it significantly prolonged the elimination half-life of metoprolol. In contrast, it did not significantly affect the pharmacokinetics of atenolol. Propranolol significantly decreased the resting pulse rate after diltiazem pretreatment as compared to placebo. The results indicate that diltiazem impaired the clearance of propranolol and metoprolol, which are principally metabolized by an oxidative pathway, and that the kinetic interaction between diltiazem and propranolol may partly be related to the significant reduction in the pulse rate produced by the latter.
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  • 123
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    European journal of clinical pharmacology 36 (1989), S. 79-82 
    ISSN: 1432-1041
    Keywords: cefonicid ; paediatric infections ; pharmacokinetics ; single dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of cefonicid was studied in 17 children requiring antibiotic treatment for respiratory or urinary tract infections. After informed consent had been obtained from the parents, a single dose of cefonicid 50 mg/kg/body weight was given by intramuscular injection. The mean peak serum concentration of 212.63 µg/ml was reached at 1.00 h, as absorption occurred at a very fast rate with a mean constant of 3.24 h−1. Mean values for half-life, apparent volume of distribution (Vz), total body clearance (CL), and renal clearance (CLR) were 3.24 h, 0.21 l·kg−1, 16.67 ml·min−1 and 13.60 ml·min−1 respectively. There was an inverse relationship between age and Vz, whereas CL and CLR were positively correlated with age. Cefonicid concentrations in urine were many times higher than the MICs of susceptible strains of bacteria. The study demonstrated that i.m. cefonicid 50 mg·kg−1 gave serum concentrations well within the therapeutic range for susceptible bacteria, and that its pharmacokinetic properties allow single daily doses to be used to treat infections in children.
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  • 124
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    European journal of clinical pharmacology 36 (1989), S. 103-109 
    ISSN: 1432-1041
    Keywords: asthma ; chronopharmacology ; theophylline ; circadian rhythms ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
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  • 125
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    European journal of clinical pharmacology 36 (1989), S. 205-208 
    ISSN: 1432-1041
    Keywords: amlodipine ; pharmacokinetics ; renal-impairment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Amlodipine was administered as 14 single 5-mg oral daily doses to 27 male subjects with renal function ranging from normal to haemodialysis-dependent. Blood specimens were obtained for measurement of plasma amlodipine concentrations for 24 h following the first dose, for 168 h following the final dose and during daily administration of amlodipine. Amlodipine was well tolerated. Renal impairment had little effect on the pharmacokinetics of amlodipine. The elimination half-life was of the order of 50 h, similar to previously reported values and did not vary with renal function. Steady-state pre-dose concentrations were observed after the ninth dose. Accumulation of amlodipine was not significantly different from that expected on theoretical grounds and did not significantly change with renal function. These results suggest that once daily administration of amlodipine is suitable for all degrees of renal function and that dosage adjustment is not necessary in renal impairment.
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  • 126
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    European journal of clinical pharmacology 36 (1989), S. 209-211 
    ISSN: 1432-1041
    Keywords: naproxen ; transcutaneous absortion ; non-steroidal anti-inflammatory drug ; topical application ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of naproxen was studied in healthy volunteers after cutaneous application of gels containing 5 and 10% of the drug. Bioavailability was estimated from serum concentration and cumulative urinary metabolite excretion data, both determined up to 96 hours after drug administration. The mean bioavailability after the 10% gel was 1.1% (serum data) and 1.0% (urine data), and after the 5% gel it was 2.1% (serum data) and 1.8% (urine data). Despite the small amount of naproxen absorbed, a potential pharmacological effect, due to cutaneous accumulation of the drug following topical administration, may be suggested from the course of the serum concentration-time curves.
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  • 127
    ISSN: 1432-1041
    Keywords: nimodipine ; pharmacokinetics ; haemodynamics ; cardiopulmonary resuscitation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary As the pharmacokinetics of a drug may be altered in haemodynamically compromised patients, the plasma concentrations and haemodynamic effects of the calcium entry blocker nimodipine have been examined in patients resuscitated after out-of-hospital cardiac arrest. In 7 patients nimodipine was infused at increasing rates up to 30 µg·kg−1·h−1. The plasma concentrations increased with increasing dose; at the highest dose a mean steady-state plasma concentration of 22.1 ng·ml−1 was obtained, and the mean plasma clearance was 1.4 l·kg−1·h−1. There were no marked changes in mean arterial blood pressure or heart rate. In 9 other patients nimodipine was given as a bolus infusion of 10 µg·kg−1 over 3 min, followed by a continuous infusion of 30 µg·kg−1·h−1. A mean steady-state plasma concentration of 17.6 ng·ml−1 was obtained and the mean plasma clearance was 1.9 l·kg−1·h−1. Heart rate did not change significantly, but the mean arterial blood pressure fell. The data indicate that in patients resuscitated after cardiac arrest, the pharmacokinetics of nimodipine are not markedly different from patients with other conditions, e.g. subarachnoid haemorrhage. However, if a loading dose is given to obtain a steady-state concentration sooner, there will be a fall in arterial blood pressure.
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  • 128
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    European journal of clinical pharmacology 36 (1989), S. 361-367 
    ISSN: 1432-1041
    Keywords: cimetidine ; burned children ; stress ulceration ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the mechanisms of the increased dosage requirements of the H2-receptor antagonist cimetidine in paediatric burned patients in a pharmacokinetic and pharmacodynamic study. Cimetidine (10–15 mg·kg−1) was given to 21 burned children and multiple blood samples were obtained for determination of plasma cimetidine concentrations and pharmacokinetic analysis. The relation of gastric pH to plasma cimetidine concentrations was studied in five of these children who had nasogastric tubes. In an additional four patients the effects of cimetidine on gastric pH were studied during a continuous infusion of cimetidine, which maintained steady-state plasma cimetidine concentrations above 0.5 µg·ml−1. The mean (SEM) clearance of cimetidine in burned children was 16.22 ml·kg−1 and cimetidine half-life was 1.06 h. The cimetidine clearance and half-life values were significantly higher in burned children compared with our previously reported values for normal adult patients, 8.2 ml·min·kg−1 and 2.21 h respectively. Endogenous creatinine clearance normalized to 70 kg in burned children was 190 ml·min−1. In burned children 41% of the dose of intact cimetidine was excreted during 8 h of the study compared with 45% excretion during 24 h in healthy adult controls previously reported. The correlation coefficient between creatinine and cimetidine clearances was 0.93 (r 2=0.85). The plasma concentration of cimetidine needed to increase gastric pH to ≥4.0 was ≥1.0 µg·ml−1, which contrasts with the value of 〉0.5 µg·ml−1 required for adult burned patients. These findings support the hypothesis that the higher dosage requirements of cimetidine in burned children is due both to enhanced elimination kinetics and to alterations in target organ sensitivity, requiring higher than normal plasma concentrations for the desired effect. In burned children Cimetidine should be given in higher doses and/or more frequently.
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  • 129
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    European journal of clinical pharmacology 36 (1989), S. 375-378 
    ISSN: 1432-1041
    Keywords: mexiletine ; cimetidine ; ranitidine ; pharmacokinetics ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of mexiletine, a Class I antiarrhythmic drug, was investigated in 6 healthy volunteers after single oral doses and 15 min intravenous infusions of 3 mg/kg. Cimetidine and ranitidine are commonly used H2-receptor antagonists, which interact adversely with many drugs, e.g. inhibition of the metabolism of Class I antiarrhythmics such as lidocaine and quinidine by cimetidine. To investigate the effects of the two drugs on the kinetics of mexiletine, cimetidine 800 mg·day−1 or ranitidine 600 mg·day−1 were administered orally for one week. Neither H2-receptor antagonist altered the distribution and elimination of mexiletine, nor did they affect its overall kinetics, or excretion of the metabolites para- and 4-OH-methylmexiletine after oral and intravenous administration of mexiletine.
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  • 130
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    European journal of clinical pharmacology 36 (1989), S. 383-388 
    ISSN: 1432-1041
    Keywords: naproxen ; sustained-release formulation ; pharmacokinetics ; bioavailability ; efficacy ; tolerability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and clinical efficacy of a once-daily sustained-release formulation of naproxen (sodium salt) have been compared with those of conventional-release agents. In a single dose pharmacokinetic study, the rate of absorption of the sustained-release preparation was less than that of a conventional-release preparation but the extent of absorption was the same. As is the case with conventional-release naproxen, food decreased the rate but not the extent of absorption of the sustained-release formulation. On multiple dose administration for 7 days, the AUC and average concentrations of the sustained release preparation (1 g daily) were the same as those for conventional release preparations of naproxen sodium (250 mg four times daily) and naproxen free acid (500 mg daily). The conventional-release sodium salt was absorbed more quickly with no differences in bioavailability. A double-blind clinical comparison in patients with osteoarthritis showed the sustained-release preparation (1 g daily) to be equivalent in efficacy to conventional naproxen capsules (500 mg twice daily) but to have a significantly lower incidence of gastrointestinal side-effects. The results suggest that sustained-release naproxen sodium has potential for use as a once-daily treatment for inflammatory disease.
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  • 131
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    European journal of clinical pharmacology 36 (1989), S. 389-393 
    ISSN: 1432-1041
    Keywords: ornidazole ; haemodialysis ; pharmacokinetics ; renal function ; metabolism ; urine concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of ornidazole was studied in 6 patients treated by haemodialysis and in 8 subjects with a creatinine clearance between 4 and 99 ml/min × 1.73 m2. Blood and urine collections were performed for 72 h after i.v. and oral administration of 1.0 g ornidazole. Total body clearance, half-life, volume of distribution and systemic availability were independent of renal function and did not differ from previously reported values in normal volunteers. The haemodialysis clearance of ornidazole was 〉100% higher than the total body clearance. The renal clearance of ornidazole accounted for less than 7% of the total body clearance. The percentage of the dose of ornidazole recovered in urine as parent compound or as the biologically active metabolites [α-(chloromethyl)-2 hydroxymethyl-5 nitroimidazole-1 ethanol and 3-(2 methyl-5 nitroimidazole-1-yl)1,2 propanediol] decreased linearly with decreasing renal function. Although the sum of those three compounds recovered in urine accounted for less than 10% of the total dose of ornidazole administered, they yielded therapeutic concentrations (〉4 µg/ml) in urine over 24 h after dosing. Due to the peculiar pharmacokinetic behaviour of ornidazole, i.e. high haemodialysis clearance in the absence of significant renal clearance, no dosage adjustment is necessary while renal function declines, but an increased dose is mandatory while patients are on dialysis.
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  • 132
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    European journal of clinical pharmacology 36 (1989), S. 395-400 
    ISSN: 1432-1041
    Keywords: pyrazinamide ; antituberculous chemotherapy ; pharmacokinetics ; xanthine oxidase ; microsomal deaminase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma and urine pharmacokinetic parameters of pyrazinamide and of its metabolites (pyrazinoic acid, 5-hydroxy-pyrazinamide, 5-hydroxy-pyrazinoic acid and pyrazinuric acid) have been studied after a single oral dose of pyrazinamide 27 mg · kg−1 in 9 healthy subjects. Pyrazinamide was rapidly absorbed (tmax ≤1 h) and showed a short distribution phase followed by an elimination phase of t1/2β=9.6 h. The close similarity of the apparent elimination rates of the metabolites led to a second trial of a single oral dose of pyrazinoic acid to evaluate the formation and elimination stages. The limiting factor was found to be the activity of a microsomal deamidase (pyrazinoic acid formation from pyrazinamide and 5-hydroxy-pyrazinoic acid formation from 5-hydroxy-pyrazinamide). In contrast, oxidation by xanthine oxidase occurred very rapidly (5-hydroxy-pyrazinamide formation and pyrazinoic acid catabolism to 5-hydroxy-pyrazinoic acid).
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  • 133
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    European journal of clinical pharmacology 36 (1989), S. 423-426 
    ISSN: 1432-1041
    Keywords: itraconazole ; antifungal drug ; pharmacokinetics ; systemic availability ; dose-dependency ; food effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the influence of food and dose (50, 100, 200 mg) on the oral systemic availability of the broad spectrum antifungal itraconazole and the pharmacokinetics after repeated dosing of 100 mg in six healthy volunteers. The relative systemic availability of itraconazole capsules compared with solution averaged 39.8% in the fasting state but 102% in the post-prandial state. Food did not significantly affect the tmax of the capsules. Itraconazole AUC at single doses of 50, 100, and 200 mg had a ratio of 0.3:1:2.7, and the steady-state AUC (0–24) after 15 days of 100 mg was five times the single-dose AUC. These findings suggest non-linear itraconazole pharmacokinetics in the range of therapeutically used doses. Furthermore, capsules should be given shortly after a meal to ensure optimal oral systemic availability.
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  • 134
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    European journal of clinical pharmacology 36 (1989), S. 433-437 
    ISSN: 1432-1041
    Keywords: nitrendipine ; renal failure ; haemodynamic effects ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In sixteen patients with arterial hypertension and differing degrees of renal function the pharmacokinetics and haemodynamic effects of nitrendipine have been studied after treatment for 7 days. The AUC (0–24) and the elimination half-life of nitrendipine were significantly increased; the AUC (0–24) in patients with renal failure (median creatinine clearance 27.1 ml × min−1) was 196 ng × ml−1 × h compared to 97.8 ng × ml−1 × h in control subjects (median creatinine clearance 94.4 ml × min−1). The corresponding elimination half-lives were 13.5 h in renal failure and 4.4 h in the controls. The haemodynamic effects of nitrendipine were not enhanced in the patients.
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  • 135
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    European journal of clinical pharmacology 37 (1989), S. 313-316 
    ISSN: 1432-1041
    Keywords: diprafenone ; pharmacokinetics ; bioavailability ; first-pass metabolism ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of the antiarrhythmic drug diprafenone have been investigated in 6 healthy volunteers following single intravenous (50 mg) and oral doses (50 and 150 mg). Diprafenone was mainly eliminated by metabolism in the liver. Following i.v. infusion of 50 mg diprafenone, the terminal half-life of elimination was 1.50 h, the volume of distribution at steady-state was 1.23 l·kg−1, and the free fraction in plasma was 1.68%. Mean total plasma clearance was 741 ml·min−1·70 kg−1, which approaches normal liver blood flow after correction for the blood/plasma concentration ratio. Thus, diprafenone can be classified as a high extraction drug. Following oral administration, a dose-dependent increase in bioavailability from 10.9 (50 mg dose) to 32.5% (150 mg dose) was observed. The data suggest that diprafenone is subject to saturable hepatic first-pass metabolism.
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  • 136
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    European journal of clinical pharmacology 37 (1989), S. 321-322 
    ISSN: 1432-1041
    Keywords: cyclosporin ; synovial fluid ; rheumatoid arthritis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
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  • 137
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    European journal of clinical pharmacology 37 (1989), S. 387-389 
    ISSN: 1432-1041
    Keywords: salbutamol ; pharmacokinetics ; renal insufficiency ; biological effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Salbutamol was administered intravenously to 5 patients with renal function impairment for estimation its pharmacokinetic parameters. The mean terminal half-life was 256 min, similar to previously reported values in healthy adults. The mean clearance (167 ml/min) and the mean volume of distribution (55 l) were decreased. These parameters were not correlated with the creatinine clearance. A slight but significant decrease was observed in the plasma potassium level up to 125 min after the salbutamol infusion. The heart rate was significantly increased, and the increase in 3 patients was correlated with the salbutamol concentration. The biological effects of the drug were less marked than expected.
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  • 138
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    European journal of clinical pharmacology 36 (1989), S. 613-616 
    ISSN: 1432-1041
    Keywords: ceftriaxone ; cefotaxime ; cirrhosis ; pharmacokinetics ; ascites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have compared in two separate studies the kinetics of ceftriaxone and cefotaxime in 8 cirrhotic patients with ascites and 8 control subjects after a single 20 min intravenous infusion of 1 g of each drug. The apparent volumes of distribution (Vz) were found to be significantly higher in cirrhotics than in control subjects (0.87, versus 0.49, l·kg−1, for cefotaxime and 0.23 versus 0.13 for ceftriaxone). The elimination kinetics of ceftriaxone were similar in the two groups. In contrast, the total and non-renal clearances of cefotaxime were reduced in cirrhotic patients. The two drugs rapidly entered the ascitic fluid. Peritoneal concentrations of ceftriaxone were higher than 7 µg·ml−1 from the second hour after the infusion and were 8.9 µg·ml−1 at 24 h. Peritoneal concentrations of cefotaxime were higher than 4 µg·ml−1 from 0.5 to 8 h after the infusion.
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  • 139
    ISSN: 1432-1041
    Keywords: indomethacin ; diflunisal ; pharmacokinetics ; drug interaction ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The single-dose pharmacokinetics of indomethacin following 100 mg rectally was measured in two groups of 8 healthy subjects before and after diflunisal 500 mg p.o. once daily, or 500 mg in the morning and 1000 mg in the evening, until steady state conditions were reached. A further group of 8 healthy subjects was given 50 mg indomethacin rectally before and after diflunisal 500 mg p.o. twice daily. High dose diflunisal (1500 mg/day) decreased the renal clearance of indomethacin from 21.9 to 1.8 ml/min (92%) and reduced the renal excretion of both unchanged (63%) and conjugated (82%) indomethacin. The apparent total body clearance (0.12 l/h/kg), apparent volume of distribution (0.98 l/kg), and volume of distribution at steady state (0.80 l/kg) were decreased by 47%, 35% and 30%. The maximum plasma concentration (2.4 µg/ml) and total area under the curve (13.0 µg × h/ml) were increased by 40% and 119%, respectively. The terminal elimination half-life (5.7 h) and mean residence time (6.7 h) were slightly prolonged (7.0 h and 8.8 h) in the presence of diflunisal. The contribution of metabolism to the overall elimination of indomethacin was increased by only 2%. Similar results were obtained when the subjects were challenged with the low dose of diflunisal (500 mg/day), although the magnitude of the changes were smaller. The interaction between indomethacin and diflunisal may be due to competition both at the metabolic (conjugation) and the excretory (tubular secretion) levels. When the subjects were given 50 mg indomethacin and diflunisal 1000 mg/day simultaneously, the achieved maximum plasma concentration of indomethacin (2.53 µg/ml) was comparable to that seen after 100 mg in the absence of diflunisal (3.1 µg/ml), but the AUC was greater (21.7 µg × h/ml vs 13.0 µg × h/ml). Adverse central nervous reactions were more frequent and more pronounced at higher plasma indomethacin concentrations.
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  • 140
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    European journal of clinical pharmacology 37 (1989), S. 595-598 
    ISSN: 1432-1041
    Keywords: amitriptyline ; nortriptyline ; pharmacokinetics ; linear kinetics ; depressed patients ; toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The linearity of the (AMT) kinetics of amitriptyline has been tested in 135 depressed dosed twice daily by measuring plasma. Their (AMT) and nortriptyline (NT) levels under steady-state conditions. The AMT concentration/dose ratios at low and high dosages were not significantly different and there was a linear relationship between the dose ratios and the concentration ratios. No change in the metabolic ratio (AMT/NT) was observed between the two dosages. Although the results are consistent with linear AMT kinetics, there may have been nonlinear kinetics in some patients as the ratio between the concentration/dose ratios in them at low and high dosages was greater than one. Those patients were characterized by a low concentration/dose ratio at low dosage. No clinical adverse effect appeared in the study.
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  • 141
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    European journal of clinical pharmacology 37 (1989), S. 97-100 
    ISSN: 1432-1041
    Keywords: theophylline ; sex differences ; pharmacokinetics ; gender
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Theophylline pharmacokinetic parameters were compared in healthy males and healthy premenopausal females who were matched for age and smoking status. Twenty-four subjects (including five smokers and seven non-smokers of each sex) received a single dose of aminophylline 6 mg·kg−1, orally or by intravenous infusion. Theophylline half-life was significantly shorter in female non-smokers (FNS) versus male non-smokers (MNS), (FNS=6.0 h; MNS=9.3 h), and in female smokers (FS) versus male smokers (MS), (FS=4.6 h; MS=6.3 h). Total body clearance was significantly different in FNS versus MNS, (FNS=43.8 ml·min−1·−1.73 m−2; MNS=37.4 ml·min−1·1.73 m−2), but did not reach statistical significance in FS vs. MS, (FS=64.2 ml·min−1·l−1·1.73 m−2; MS=53.1 ml·min−1·1.73 m−2). Volume of distribution did not differ significantly between groups. Sex differences in theophylline pharmacokinetics exist and may reflect differences in drug metabolism.
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  • 142
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    European journal of clinical pharmacology 37 (1989), S. 173-180 
    ISSN: 1432-1041
    Keywords: frusemide ; nephrotic syndrome ; albumin ; dextran ; pharmacokinetics ; renin-angiotensin-aldosterone system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The renal handling and effects of an intravenous bolus of frusemide with and without plasma volume expansion with dextran or albumin, and with large variations in plasma albumin concentration, have been studied in five patients with the nephrotic syndrome. Decreased renal sensitivity to frusemide was found in only one patient, who also had hypovolaemia and an activated renin-angiotensin-aldosterone system. Plasma volume expansion increased the diuresis but not the saluresis, and slightly increased renal sensitivity to frusemide. An increase in albuminuria after albumin infusion did not reduce the sensitivity to frusemide. A decrease in plasma albumin concentration from 33 g·l−1 after albumin infusion to 23 g·l−1 after infusion of dextran caused a substantial increase in the renal clearance (from 84 to 123 ml·min−1), non-renal clearance (from 72 to 138 ml·min−1), and apparent volume of distribution (from 13 to 23 l) of frusemide, probably as a consequence of an increase in the unbound fraction. The rate of urinary excretion of frusemide was highest after albumin infusion, despite the fact that its renal clearance was lowest then.
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  • 143
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    European journal of clinical pharmacology 37 (1989), S. 181-184 
    ISSN: 1432-1041
    Keywords: baclofen ; renal function ; healthy subjects ; pharmacokinetics ; probenecid ; tubular secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Baclofen, a centrally acting muscle relaxant, is used in the treatment of spasticity. Its pharmacokinetics has been derived from plasma and urine data in four healthy subjects, whose renal function was simultaneously measured. After oral administration of a single 40 mg dose, baclofen was mainly excreted unchanged by the kidney, 69 (14) %. The half-life, calculated from extended least squares modelling (ELSMOS) both of plasma and urine data was 6.80 (0.68) h, which is longer than reported in most studies based solely on plasma data. The renal excretion rate constant had the high mean value of 0.35 (0.24) h−1, and the apparent renal clearance of baclofen equalled the creatinine clearance. Passive tubular reabsorption is relatively unimportant, since no dependence was observed on variables urine flow or pH. Although active tubular secretion may contribute to its renal clearance, as shown by the effect of coadministration of probenecid, glomerular filtration appears to be the dominant transport mechanism.
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  • 144
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    European journal of clinical pharmacology 37 (1989), S. 193-194 
    ISSN: 1432-1041
    Keywords: urapidil ; digoxin ; blood drug level ; pharmacokinetics ; drug absorption/-interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In an open, randomized, two-period change-over study the effect of urapidil, an antihypertensive agent, on steady-state serum digoxin levels was investgated in 12 healthy male volunteers. The subjects were given digoxin 0.25 mg once daily for 4 days to produce a steady-state digoxin level in serum. At the end of that time the subjects received either digoxin monotherapy or digoxin and concomitant treatment with urapidil 60 mg b.d. for a further 4 days. Subsequently the treatments were changed over. The absorption characteristics Cmax and tmax of digoxin were not altered by concomitant urapidil treatment. The geometric mean and nonparametric 95% confidence limits of digoxin relative bioavailability were 97% (93%–103%). Therefore, concomitant administration of urapidil with digoxin treatments did not appear to alter the rate and extent of absorption of the glycoside.
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  • 145
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    European journal of clinical pharmacology 37 (1989), S. 185-189 
    ISSN: 1432-1041
    Keywords: nifedipine ; renal failure ; pharmacokinetics ; protein binding ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The total and free steady-state plasma levels of nifedipine in patients with renal failure have been compared with those in subjects with normal renal function. Studies were done after administration of nifedipine 10 mg t.d.s. p.o. for 5 days, after i.v. infusion of 4·4 mg, and after a single 10 mg oral dose. The systemic clearance of nifedipine after a single i.v.-dose was higher in subjects with renal insufficiency (854 ml/min) than in those with normal renal function (468 ml/min). After the single oral dose the AUC (6100 ng·min·ml−1) and maximum plasma concentration (75.0 ng·ml−1) were lower than in subjects with normal renal function (19300 ng·ml−1; 122 ng·ml−1). The plasma protein binding of nifedipine averaged 95.5% in normal subjects and 94.8% in patients with renal failure. Although free and total steady-state plasma levels of nifedipine tended to be somewhat lower than normal in renal failure, the changes in pharmacokinetics and decreased protein binding of nifedipine did not result in a significantly different steady-state plasma level of the drug. The blood pressure response to a given plasma nifedipine level appeared to be enhanced in renal failure.
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    European journal of clinical pharmacology 37 (1989), S. 501-506 
    ISSN: 1432-1041
    Keywords: N-acetylcysteine ; paracetamol ; acetaminophen overdose ; pharmacokinetics ; liver damage ; adverse reactions ; dose modifications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Seventeen patients received standard treatment with intravenous N-acetylcysteine for 18 episodes of severe poisoning with paracetamol (acetaminophen). The dose of N-acetylcysteine was 150 mg/kg given in 15 min followed by 50 mg/kg in 4 h and 100 mg/kg over the next 16 h. Liver damage was absent or mild on 13 occasions (ALT〈500 µ/l) and severe on 5 (ALT〉1000 µ/l). Total plasma N-acetylcysteine was estimated by HPLC. The mean maximum plasma concentration after the initial loading dose was 554 mg/l. Concentrations then fell rapidly and after 12 h a mean steady-state level of about 35 mg/l was maintained. When the infusion was discontinued N-acetylcysteine disappeared with a half-life of 5.7 h. The mean steady-state volume of distribution, AUC, mean residence time and total clearance were 536 ml/kg, 1748 mg·h·l−1, 2.91 h and 3.18 ml·min−1·kg−1. These values are generally consistent with those previously reported with much smaller doses and the disposition of N-acetylcysteine does not appear to be dose-dependent. The elimination of N-acetylcysteine was not impaired in the patients with severe liver damage, and the pharmacokinetic variables and plasma concentrations were similar in patients with and without hepatotoxicity. The dosage schedule for intravenous N-acetylcysteine should probably be modified since adverse reactions invariably occur early when plasma concentrations are at their highest, and liver damage was prevented just as effectively at the lowest as at the highest Cmax. High initial concentrations of N-acetylcysteine can be avoided with simple alternative regimens based on the kinetic data of this study.
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  • 147
    ISSN: 1432-1041
    Keywords: oxitropium bromide ; pharmacokinetics ; radioreceptor assay ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Oxitropium bromide (OXBR) is a new anticholinergic drug, which is expected to be useful in the treatment of nocturnal asthma. The only pharmacokinetic data were obtained with the14C-labelled compound. A sensitive radioreceptor assay for the determination of unlabelled OXBR in plasma was developed, based on competition between OXBR and3H-N-methylscopolamine for binding to muscarinic receptors. OXBR was isolated from plasma by ion-pair extraction and re-extraction. Active metabolites present in significant amounts might interfere in the assay, but this was not the case for OXBR metabolites. Detection limits were 300 pg·ml−1 and 3 ng·ml−1 for plasma and urine, respectively. For the latter no extraction step was required. The single dose pharmacokinetics of OXBR was studied following inhalation (3 mg), oral (2 mg) and i.v. (1 mg) administration to 12 men, following an open, cross-over design. After i.v. administration the kinetic parameters were: Vc 38.4 l; t1/2α 5.3 min; t1/2β 142 min; AUC 8.9 h·ng·ml−1; renal excretion 50.2%, k10 3.5 l·h−1 and total clearance 1874 ml/min. The apparent bioavailabilities were 0.48% and 12.4% by the oral and inhalation routes, respectively, based on the cumulative renal excretion. There were moderate adverse reactions due to the anticholinergic properties of the drug.
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  • 148
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    European journal of clinical pharmacology 37 (1989), S. 533-536 
    ISSN: 1432-1041
    Keywords: bismuth ; absorption ; elimination ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of bismuth subcitrate were studied in plasma and urine under conditions of single and multiple dosing (28–56 days) using atomic absorption technique. Single dose plasma pharmacokinetics showed peak concentrations of 5.5–57.5 µg·l−1 (mean=24.7 µg·l−1), reached between 30 and 60 min post dosing with an apparent biphasic elimination pattern. Multiple dose studies showed a continuing rise in plasma concentration and urine excretion rate reaching apparent steady-state levels over 7–29 days (mean=18 days). Washout studies in 6 individuals reciprocated accumulation. Maximum equilibrated plasma levels of 7.6–58.3 µg·l−1 (mean=38.3 µg·l−1) were well below those associated with encephalopathy. The half-life of bismuth elimination was 20.7 days. Present patterns of intermittent dosing with bismuth are unlikely to be associated with bismuth accumulation despite slow accumulation and elimination.
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  • 149
    ISSN: 1432-1041
    Keywords: salbutamol ; asthma ; controlled-release formulation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Fifteen patients with asthma were given salbutamol controlled-release (SCR) 4 mg or 8 mg twice daily for seven days, in a randomised double-blind cross-over design. Plasma salbutamol levels were measured after the first and fifteenth doses for a 12 h period following drug ingestion. At steady-state the geometric mean values for Cmax were 8.2 ng/ml for 4 mg, and 16.1 ng/ml for 8 mg. Median tmax values were 300 and 240 min respectively. The geometric mean AUC (0–12) were 4507 ng·min·ml−1 and 8980 ng·min/ml. Peak to trough fluctuation ratios were 0.577 and 0.572. There were no significant differences between 4 mg or 8 mg formulations, for any of the parameters measured, after appropriate corrections for dose. The concentration-time profiles at steady-state showed little fluctuation in plasma salbutamol levels over the twelve hour dosing interval. These results show that 4 mg and 8 mg formulations of SCR provide smooth plasma profiles at steady-state with a twice daily dosing regime.
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  • 150
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    European journal of clinical pharmacology 37 (1989), S. 69-74 
    ISSN: 1432-1041
    Keywords: oxcarbazepine ; pharmacokinetics ; drug metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of oxcarbazepine (a new anticonvulsant which is a congener of carbamazepine) and of its 10-hydroxy metabolite were studied at the outset of therapy in 8 adult epileptics comedicated with other anticonvulsants. The pharmacokinetic study was repeated under steady-state conditions after 3 months of drug intake in 6 of these subjects. The plasma elimination half-life of oxcarbazepine appeared to lie in the range 1.0–2.5 h, and that of its 10-hydroxy metabolite averaged 8.4 h. The apparent oral clearance of the parent drug (averaging 2.51·kg−1·h−1) was high enough to suggest substantial presystemic elimination. The oral clearance fell after 3 months of drug intake, but the half-lives of the drug and metabolite showed no statistically significant change over this time. Steady-state plasma levels of both drug and metabolite were linearly related to drug dose, metabolite levels averaging 9 times those of the parent substance.
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  • 151
    ISSN: 1432-1041
    Keywords: alfuzosin ; prazosin ; alpha1-adrenoceptor antagonist ; noradrenaline ; pharmacokinetics ; pharmacodynamics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In an open dose ranging study with random inclusion of placebo, alfuzosin (α1-adrenoceptor antagonist) 1, 2.5 and 5 mg was administered to 6 healthy volunteers, 3 of the volunteers received 10 mg alfuzosin. Supine systolic blood (SBP) pressure was not reduced by alfuzosin although significant increases occurred in supine heart rate (HR) after 2.5 and 5 mg. In the standing position, SBP was reduced at 2 and 4 h with 5 mg alfuzosin; significant increases in HR occurred following 1, 2.5 and 5 mg at 2, 4, 6 and 8 h after administration. Exercise SBP was not reduced; diastolic blood pressure was significantly reduced at 4 and 6 h with 5 mg alfuzosin. More marked effects were seen in the 3 subjects who received 10 mg alfuzosin. After 1 and 5 mg, tmax ranged from 1–2 h; Cmax (4.1 to 20.8 ng · ml−1; AUC (0–24) 20 to 132 ng · ml−1 · h (1 and 5 mg respectively) increased progressively with dose indicating dose dependent kinetics; no significant changes occurred in the visual analogue scale for sedation. A comparison of alfuzosin 5 mg, prazosin 1 mg and placebo each administered for 4 days, indicated that alfuzosin did not significantly reduce standing SBP on either Day 1 or Day 4; prazosin reduced SBP at 2 and 4 h on Day 1 and 6 h on Day 4 compared to placebo. Standing HR was increased by alfuzosin at 2 h on Day 1 and Day 4; increases occurred with prazosin at 2, 4, 6 and 8 h on Day 1 and 6 h on Day 4. Supine plasma noradrenaline increased with alfuzosin and prazosin at 2 and 4 h on Days 1 and 4; the increases were not significantly different. The plasma elimination half-life (t1/2) for alfuzosin was 3.4 h and 3.1 h after acute and chronic administration; (t1/2) for prazosin was 2.6 and 2.9 h. In conclusion alfuzosin causes small reductions in systolic blood pressure, accompanied by a dose dependent increase in heart rate in the supine and standing position and following exercise.
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  • 152
    ISSN: 1432-1041
    Keywords: acetyl-L-carnitine ; renal clearance ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of acetyl-L-carnitine hydrochloride were investigated in 6 healthy volunteers of both sexes after i.v. injection of 500 mg of the drug, expressed as inner salt. Plasma concentrations and urinary excretion of acetyl-L-carnitine (A), L-carnitine (B) and total acid soluble L-carnitine fraction were evaluated over a period lasting from 24 h before to 48 h after the administration. Plasma concentrations of A increased quickly after administration and then declined reaching base values within 12 h. Conversely, plasma concentrations of B rose more slowly, reaching a peak in 30–60 min, and then declined to base values within 24 h. Most of the injected dose of acetyl-L-carnitine was recovered in the urine during the first 24 h after administration as B and A. Mean renal clearance of both A and B during the first 12 h after injection was higher than the base values, suggesting the presence of a saturable tubular reabsorption process which may counterbalance major changes occurring in plasma concentrations of L-carnitine pattern.
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  • 153
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    European journal of clinical pharmacology 37 (1989), S. 75-77 
    ISSN: 1432-1041
    Keywords: dexamethasone ; congenital adrenal hyperplasia ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of dexamethasone, given at low dose, were studied in 13 patients with congenital adrenal hyperplasia (CAH) to ascertain whether kinetics differed in this inherited disorder of cortisol metabolism from those seen in healthy individuals. Changes in plasma dexamethasone concentration after intravenous bolus, measured using a simple novel radioimmunoassay, were well described by a two-compartment open model with first-order kinetics. Values for λ2: 0.206 h−1, t1/2: 3.53 h, Vc: 24.41 and f: 0.64 were similar to those previously reported for normal subjects. There were considerable interindividual differences in parameter values and Cmaxp.o. (range 22–67 nmol/l). As suppression of the hypothalamo-pituitary-adrenal axis correlates with plasma dexamethasone levels, this variability may partly explain the differing dose and dose schedule requirements necessary to achieve adequate therapeutic control in the clinical management of CAH.
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  • 154
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    European journal of clinical pharmacology 37 (1989), S. 79-84 
    ISSN: 1432-1041
    Keywords: colchicine ; pharmacokinetics ; oral administration ; zero-order absorption ; systemic availability ; dose dependency ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of colchicine has been studied in nine healthy male volunteers after oral doses of 0.5, 1, and 1.5 mg as tablets. Plasma and urine samples were collected over 48 h and analysed for colchicine by radioimmunoassay. Individual colchicine concentration profiles in plasma and urine were well described by a two-compartment open model with zero-order input. Considering the absorption variables as specific to each experiment, the lag time (0–0.35 h) and duration (0.39–2.38 h) of absorption were found to be independent of dose, while the zero-order rate constant of absorption (k0) increased linearly with dose. Disposition variables were taken as common to the three experiments, except in six subjects in whom renal excretion varied significantly across experiments in a dose-independent manner. For seven subjects the terminal half-life was 19.4 h, the oral apparent volume of distribution at steady-state (Vss/f) was 691 l, and the oral systemic clearance (CL/f) was 33.1 l·h−1. In the two other subjects, the values were unreliable, but the estimated terminal half-life was greater than 48 h, Vss/f ranged from 1690 to 3480 l, and CL/f was in the range of the other subjects in 1 subject, and it was about 15l·h−1 in the other. In the latter subject, these estimates, together with the observation that plasma concentration reached a plateau at 2 to 5 h after ingestion, suggest enterohepatic cycling of colchicine. Overall, the disposition of colchicine was linear in the dose range 0.5–1.5 mg, with a long terminal half-life, and absorption obeyed zero-order kinetics, with k0 proportional to dose.
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  • 155
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    European journal of clinical pharmacology 37 (1989), S. 85-90 
    ISSN: 1432-1041
    Keywords: theophylline ; sustained-release formulation ; bioavailability ; fatty food ; dumping effect ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A cross-over study of kinetics has been undertaken in 12 healthy adults volunteers using two sustained-release theophylline products that allow once a day dosing (Theo-Dur tablets and Dilatrane A.P. bead filled capsules) to compare the i.v. pharmacokinetic profiles when taken with an hyperlipidic meal and a balanced standard meal. Each subject took part in four phases in randomised order, corresponding to all possible combinations of the products and the types of meal. Each phase involved a single dose of 9 to 11 mg·kg−1 theophylline administered at 20.00 h, at the beginning of the meal, with 100 ml water. The two formulations were found to be bioequivalent with both types of meal. Taken with a balanced meal, the mean parameters were similar; for Theo-Dur and Dilatrane A.P. they were respectively: Cmax: 11.32 mg·l−1 which plateaued from 8 to 10 h after dosing and 10.9 mg·l−1, which plateaued after 6 to 10 h; AUC 230 mg·h·l−1 and 220 mg·h·l−1; and MRT 18.2 h and 17.7 h. After the hyperlipidic meal the values for Theo-Dur and Dilatrane A.P. respectively, were: Cmax 10.9 mg·l−1 at 12 h and 11.3 mg·l−1 at 10 h; AUC 237 mg·h·l−1 and 227 mg·h·l−1; and MRT 19.2 h and 18.9 h. In spite of a decrease in the absorption rate, which led to a shift to the right of about 2 h of the plasma concentration-time curve, the bioavailability of both formulations were not significantly modified by a hyperlipidic meal as compared to a balanced meal. The shift of the curve with fatty food was not clinically important, as there was no dumping effect. The main difference between the two formulations was seen during the absorption phase, which was linear and less variable with Dilatrane A.P. and sigmoidal with Theo-Dur. This was observed with both types of meal.
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  • 156
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    European journal of clinical pharmacology 37 (1989), S. 161-166 
    ISSN: 1432-1041
    Keywords: midazolam ; benzodiazepine ; pharmacokinetics ; biotransformation ; surgery ; prolonged recovery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of midazolam has been studied in patients recovering from cardiac surgery, who required sedation for postoperative mechanical ventilation. Twelve males (mean age 64.5 years) with severe heart disease received an infusion of midazolam 15 mg·h−1 for 4 h, starting 1 to 3 h post surgery. Multiple blood samples were collected from each patient during the infusion and up to 48–93 h after it. The pharmacokinetic parameters of midazolam were determined using both moment analysis and the program NONMEM. The average terminal half-life was 10.6 h. The prolonged elimination was mainly due to a decrease in its metabolic clearance (0.25 l·min−1). The maintenance infusion dose of midazolam in such patients should be reduced. The time to recovery after stopping an infusion depends upon the amount of drug in the body at that time and a simulation of the plasma concentrations after various infusion regimens suggests that recovery will be delayed after prolonged (〉48 h) administration of midazolam to these patients. However, after shorter infusions (〈12 h), redistribution of the drug away from the site of action was still occurring and recovery would be expected to be relatively rapid.
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  • 157
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    European journal of clinical pharmacology 37 (1989), S. 589-594 
    ISSN: 1432-1041
    Keywords: ketoprofen ; probenecid ; cholecystectomy ; enantiomers ; glucuroconjugates ; stereoselectivity ; T-tube patients ; biliary excretion ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ketoprofen (KT), a 2-arylpropionic acid nonsteroidal antiinflammatory drug, is administered as a racemate. Previous reports suggest stereoselective biliary excretion of KT enantiomers. This hypothesis was tested by administering 50 mg racemic KT to five patients who required bile drainage following cholecystectomy surgery. Subsequently, to study the influence of probenecid (PB), an inhibitor of KT renal elimination, on the biliary excretion, 1000 mg PB was administered 1.5 h before KT to the same patients. The unchanged and conjugated (as glucuronides) KT enantiomers were measured in plasma, urine and bile. In general, KT enantiomers had different plasma concentration-time curves. As compared to normal subjects, these patients had comparable AUCs and shorter t1/2s. Biliary concentrations of conjugated S-KT were greater than R-KT. Nevertheless, the total cumulative biliary excretion of conjugated KT did not exceed 2% of the dose ruling out this pathway as a significant route of KT elimination. There was a positive and significant correlation between the cumulative urinary excretion of conjugated KT enantiomers and creatinine clearance. Although PB did not influence the pattern of stereoselectivity of KT, it increased AUC and prolonged t1/2 of the enantiomers. While reducing cumulative urinary excretion, PB increased total biliary elimination of conjugated KT enantiomers. This, however, did not totally compensate for the reduced urinary excretion. It is suggested that the impaired conjugation of KT caused by PB administration may result in the augmentation of other, otherwise minor, metabolic pathways.
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  • 158
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    European journal of clinical pharmacology 37 (1989), S. 613-615 
    ISSN: 1432-1041
    Keywords: verapamil ; pharmacokinetics ; circadian rhythm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Circadian variation in the metabolism of verapamil was investigated in 10 patients with stable angina pectoris during treatment with sustained-release verapamil 360 mg at 08.00 h or 22.0 h. No major difference in exercise parameters was found. During the evening dosage schedule a significantly greater bioavailability (AUC) and a prolonged time to peak concentration was found. During the night (24.00 h–06.00 h) the half-life of verapamil was significantly longer than during the day (16.00 h–22.00 h). These differences in pharmacokinetics may be due to reduced hepatic blood flow at night or to circadian variation in hepatic microsomal metabolism.
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  • 159
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    Journal of pharmacokinetics and pharmacodynamics 17 (1989), S. 327-345 
    ISSN: 1573-8744
    Keywords: enterohepatic recirculation ; pharmacokinetics ; hepatic extraction ; area under the first moment curve ; model ; bile ; mean residence time ; mean absorption time ; formulations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A physiologically realistic model of enterohepatic cycling (EHC) which includes separate liver and gallbladder compartments, discontinuous gallbladder emptying and first-order absorption from both an oral formulation and secreted bile (ka po and ka b, respectively) has been developed. The effect of EHC on area under the first-moment curve (AUMC) of drug concentration in plasma and on parameters derived from the AUMC was investigated. Unlike AUC, AUMC is dependent on the time and time-course of gallbladder emptying, increasing as the interval between gallbladder emptying increases. Consequently, mean residence time (MRT) is also a time-dependent parameter. Analytical solutions for MRTiv and MRTpo were derived. Mean absorption time (MAT = MRTpo — MRTivj is also time-dependent, contrary to findings previously published for a model of EHC with a continuous time lag. MAT is also dependent on k a po , k a b and the hepatic extraction ratio. The difference between MRT po s two formulations with unequal k a po values may deviate from the difference in the inverse of their absorption rate constants. Implications for design and interpretation of pharmacokinetic studies include (i) MAT values may be dominated by the time-course of recycling rather than the time-course of the initial absorption, depending on the extent of EHC and (ii) the unpredictable nature of the time of gallbladder emptying will contribute to intrasubject variability in derived parameters during crossover studies. Knowledge of the extent of EHC is invaluable in deciding whether modification of the in vitro release characteristics of an oral formulation will have any effect on the overall time-course of absorption in vivo. Techniques to monitor or control gallbladder emptying may be helpful for reducing variability in pharmaco-kinetic studies for compounds which are extensively cycled in bile.
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  • 160
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    Veterinary research communications 13 (1989), S. 389-394 
    ISSN: 1573-7446
    Keywords: buffalo ; carbenicillin ; pharmacokinetics ; therapeutics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The distribution half-life, elimination half-life, apparent volume of distribution and total body clearance of carbenicillin in healthy buffalo calves following a single intravenous administration (50 mg/kg) were 0.057±0.005 h, 1.688±0.11 h, 0.185±0.021 L kg-1 and 75.97±6.519 ml kg-1 h-1 respectively. A satisfactory dosage regimen for carbenicillin in buffalo calves was calculated to be 56 mg/kg followed by 52 mg/kg body weight repeated at 6 h intervals.
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  • 161
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    Journal of pharmacokinetics and pharmacodynamics 17 (1989), S. 109-123 
    ISSN: 1573-8744
    Keywords: anesthetics, gases ; pharmacokinetics ; volatile anesthetics ; inhalation agents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The theoretical groundwork for a rate constant formulation of inhaled anesthetic elimination kinetics is discussed. In an effort to simulate recent experimental results a linear flow-limited five-compartment model was used comprising lung, vessel-rich tissue, muscle, nonvisceral fat, and an additional compartment, marrow-visceral fat whose functional existence recently has been experimentally demonstrated. Hypothetical but plausible parameters for the marrow-visceral fat compartment were used. The theoretically predicted values were in good agreement with experimental results suggesting that this model is appropriate for the elimination kinetics of agents that are not metabolized to any significant degree. Simple approximate expressions for the rate constants were also derived and were in reasonable agreement with experimental results. The model was also employed to clarify the effect of anesthetic duration on subsequent elimination kinetics.
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  • 162
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    Journal of pharmacokinetics and pharmacodynamics 17 (1989), S. 347-364 
    ISSN: 1573-8744
    Keywords: hypersensitivity ; propranolol ; pharmacokinetics ; pharmacodynamics ; modeling ; β receptor ; adrenergic stimulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A pharmacokinetic/pharmacodynamic model of hypersensitivity to adrenergic stimulation following abrupt withdrawal of chronic β blockade was developed. The model employs the Hill equation, a term which describes the competition between isoproterenol and l- propranolol for β receptors, and a kinetic term which characterizes the appearance and disappearance rates of up-regulated β receptors. The model predicted peak chronotropic hyperresponsiveness to isoproterenol 48 hr following abrupt withdrawal of chronic treatment with daily propranolol doses of 160 mg, and a drug half-life of 3.5 hr. The model also predicted that increasing the dose rate and prolonging the half-life of propranolol delayed and decreased the extent of adrenergic hypersensitivity. The time-course of adrenergic hypersensitivity simulated by our model was in excellent agreement with that observed in studies which were published earlier by our laboratory. The model underestimated the extent of adrenergic hypersensitivity. The results of our simulation are consistent with a β agonist-receptor-effector system, which involves spare receptors, amplification of response by second and third messengers, and β agonist-antagonist-induced receptor regulation.
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  • 163
    ISSN: 1573-8744
    Keywords: propranolol ; pharmacokinetics ; pharmacodynamics ; myocardial contractility ; hypertensive ; rabbit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Myocardial contractility of normotensive and spontaneously hypertensive rabbits was determined following an iv bolus injection of propranolol HCl. Left ventricular pressure and dimension were used to calculate the contractility parameters of (dP/dt) max ,maximum fiber shortening velocity V cf , and the slope of the end systolic pressure-end systolic volume line (ESP-ESV line). Hypertension was induced by a methoxamine HCl iv infusion which mimicked the cardiac effects seen in essential hypertension. Propanolol caused a significant decrease in all contractility parameters (p〈0.05)within 15min after administration, with a peak effect occurring after 30–35 mins. The pharmacokinetics and pharmacodynamics of propranolol were fit using Hill's equation in conjunction with the concentration of drug in the theoretical effect compartment. The normotensive group of rabbits had a calculated EC (50) of 12.7 ng/ml, while the hypertensive group had an EC 50 of 6.9 ng/ml,indicating that the hypertensive rabbits were much more sensitive to the propranolol than the normotensive group. In addition, the normotensive group of rabbits demonstrated a much different pharmacokinetic-pharmacodynamic relationship than that of the hypertensive group, indicating that the hypertensive state of the animal has a significant effect upon the concentration-effect relationship.
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  • 164
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    Journal of pharmacokinetics and pharmacodynamics 17 (1989), S. 571-592 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; variability ; parameter estimation ; modeling ; nonlinear regression ; Wagner-Nelson method ; mixed effects models
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The impact of assay variability on pharmacokinetic modeling was investigated. Simulated replications (150) of three “individuals” resulted in 450 data sets. A one-compartment model with first-order absorption was simulated. Random assay errors of 10, 20, or 30% were introduced and the ratio of absorption rate (K a )to elimination rate (K e )constants was 2, 10, or 20. The analyst was blinded as to the rate constants chosen for the simulations. Parameter estimates from the sequential method (K e )estimated with log-linear regression followed by estimation of K a and nonlinear regression with various weighting schemes were compared. NONMEM was run on the 9 data sets as well. Assay error caused a sizable number of curves to have apparent multicompartmental distribution or complex absorption kinetic characteristics. Routinely tabulated parameters (maximum concentration, area under the curve, and, to a lesser extent, mean residence time) were consistently overestimated as assay error increased. When K a /K e =2,all methods except NONMEM underestimated K e ,overestimated K a ,and overestimated apparent volume of distribution. These significant biases increased with the magnitude of assay error. With improper weighting, nonlinear regression significantly overestimated K e when K a /K e ,=20. In general, however, the sequential approach was most biased and least precise. Although no interindividual variability was included in the simulations, estimation error caused large standard deviations to be associated with derived parameters, which would be interpreted as interindividual error in a nonsimulation environment. NONMEM, however, acceptably estimated all parameters and variabilities. Routinely applied pharmacokinetic estimation methods do not consistently provide unbiased answers. In the specific case of extended-release drug formulations, there is clearly a possibility that certain estimation methods yield K a and relative bioavailability estimates that would be imprecise and biased.
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  • 165
    ISSN: 1435-1463
    Keywords: Aminoadamantanes ; pharmacokinetics ; CNS ; membrane anisotropy ; excitability ; spinal alpha- and gamma-motoneurons
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The structure-activity relationship of two isomeric 1-aminoadamantanes, 1-C-ethylaminoadamantane (D 174) and 1-amino-3-ethyladamantane (D 175), on membrane anisotropy and the excitability of neurons was studied in the CNS of the rat and in the decerebrated cat. Mass spectrometric analysis showed that after a single, 40 mg/kg dose, D 174 and D 175 were unevenly distributed within the CNS of the rat, moreover the distribution pattern of the two substances was different. As measured by fluorescence depolarization in controls the membrane anisotropy was found to be higher in the older parts as compared with the younger parts of the CNS. After i.p. application of 40 mg/kg the membrane anisotropy was reduced in the cortex by D 174, whereas D 174 and D 175 increased the rigidity in striatal membranes. If cortical membranes were incubated with the substances, the fluidizing effect of D 174 was more prominent than that of D 175. In the decerebrated cat only D 174 in a dose of 5 mg/kg i.p. raised the discharge of spinal alpha-motoneurones significantly. The results suggest that the membrane architecture is more affected by D 174 as compared with D 175 which is reflected by a greater effect on membrane anisotropy as well as on the activity of spinal alpha-motoneurones.
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  • 166
    ISSN: 1573-7241
    Keywords: verapamil ; elderly ; pharmacokinetics ; cardiovascular effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pharmacokinetics and pharmacodynamics of verapamil were studied in 11 elderly subjects (age=79.67±4.74 years) and in 11 middle-aged subjects (age=45±11.37 years) following intravenous (IV), single oral, and long-term oral administration. Plasma verapamil concentrations were determined using high-pressure liquid chromatography (HPLC). Twenty-four hour dynamic Holter electrocardiographic (ECG) recordings were employed to study heart rate (HR) and P-R interval. No difference in plasma half-life, distribution volume, body clearance, and area under the curve (AUC) was observed between the two groups after IV and oral verapamil administration. Blood pressure (BP) and HR were significantly reduced after verapamil IV administration in the elderly group only (p〈0.05, p〈0.01, respectively). After single and long-term oral administration, variable HR and BP responses were observed in both groups. The P-R prolongation following both IV and single oral doses exhibited a delay with respect to the peak plasma concentration, inducing a definite hysteresis loop. The slope of P-R variations (using a linear pharmacodynamic model) was greater in the elderly both after IV and single oral verapamil administration, but statistical significance was obtained only after the single oral dose (p〈0.05). In the elderly group, after long-term oral administration, there was a significant prolongation of the P-R interval (p〈0.0001) with respect to the corresponding time point of the 24-hour predrug period. Such variations in pharmacodynamic parameters in the elderly did not, however, cause any clinical problem. In conclusion, verapamil seems to be well tolerated in the elderly as well as in younger patients at similar dosages. However, its use in the elderly requires careful clinical evaluation.
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  • 167
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    Cardiovascular drugs and therapy 3 (1989), S. 482-497 
    ISSN: 1573-7241
    Keywords: pharmacokinetics ; calcium antagonists ; liver disease ; renal disease ; hepatic enzymes ; metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A survey of the pharmacokinetic properties of the three prototypical calcium antagonist agents shows that they have in common a very high rate of hepatic first-pass metabolism with, in the case of verapamil and diltiazem, the formation of an active metabolite that affects the dose during chronic therapy. Therefore, the major factor altering the pharmacokinetic properties and the dose of the drug required is the capacity of the liver to metabolize the drug, which in turn depends on the hepatic blood flow and the activity of the hepatic metabolizing systems. Hence liver disease, a low cardiac output, and coadministration of certain drugs inducing or inhibiting the hepatic enzymes, all indirectly affect the pharmacokinetic properties of the calcium antagonists. There are also other potential drug interactions of a kinetic or dynamic nature that may arise. In general, renal disease has little effect on the pharmacokinetics of calcium antagonists.
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  • 168
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    Cardiovascular drugs and therapy 3 (1989), S. 711-730 
    ISSN: 1573-7241
    Keywords: cardiovascular disease ; pharmacokinetics ; antiarrhythmics ; inotropics ; betablockers ; diuretics ; antihypertensives
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The pathophysiologic changes occurring in cardiovascular disease can affect the kinetics of drugs in several different ways. The present review examines these modifications and the underlying mechanisms. The kinetics of specific agents, such as antiarrhythmic, antihypertensive, cardiotonic, and other drugs are considered, and the clinical implications are outlined. The clinician should be aware of these modifications, because they require an adjustment of the dosage regimen. A rational basis for a correct therapeutic choice can be provided by adequate knowledge of these modifications.
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  • 169
    ISSN: 1573-2592
    Keywords: Interferon-γ ; Kaposi's sarcoma ; human immunodeficiency virus (HIV) ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A Phase I study of recombinant interferon-gamma (rIFN-γ) was conducted to determine the toxicity and pharmacokinetics of this lymphokine in acquired immunodeficiency syndrome (AIDS) patients with Kaposi's sarcoma (KS). Sixteen patients with AIDS/KS were entered into a fixed-dose trial at either 0.001, 0.01, 0.1, or 1.0 mg/m2 of rIFN-γ. rIFN-γ was initially administered either as a single 24-hr continuous iv infusion or as a single im injection, followed 4 days later by a 10-day course of daily therapy by the same route. Following a 1-week washout period, this sequence of administration was then repeated, with the drug given by the alternate route. Pharmacokinetic analysis of the 1.0-mg/m2 group revealed that peak serum levels of up to 153 U/ml occurred 2–4 hr after im injection and that steady-state levels of up to 40 U/ml were reached approximately 7–12 hr after beginning iv infusion. Dose-related toxicities in this trial included fever, headache, fatigue, nausea, and hepatitis, all of which were most severe at the two highest doses. Dose-dependent depression of the total white blood-cell (WBC) count, affecting both granulocytes and lymphocytes, was the most common laboratory abnormality. Natural killer (NK)-cell activity was slightly enhanced at a dose of 0.1 mg/m2 but suppressed at 1.0 mg/m2 of drug; monocyte-mediated cytotoxicity, in contrast, was significantly increased only at the highest dose. No dose-related changes were noted in KS lesions, HLA-DR expression by peripheral blood mononuclear cells, lymphocyte blastogenesis, or the ability to culture cytomegalovirus (CMV) from body fluids. We conclude that a maximally tolerated dose (MTD) for this drug is in the range of 0.1–1.0 mg/m2 and that at least modest evidence of systemic immunomodulation may be seen when rIFN-γ is given at doses at or near this MTD.
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  • 170
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Description / Table of Contents: In this part properties and efficiency of the developed model1,2 are discussed. A variation of the parameters shows that vigorous effects are caused by the effective aggregation. All calculations show that at low conversion there are little temporal steps between the sequential aggregation steps. In the range of 5% to 20% conversion the velocity of aggregation decreases and the aggregative stability agrees with experiences given in the literature. It is shown that the calculated results are in agreement with the experimental results and therefore the presented model is a suitable possibility to describe the formation of some PVC-morphology properties.
    Notes: In der vorliegenden Arbeit werden die Eigenschaften des früher1,2 entwickelten Modells untersucht und diskutiert. Die Variation der Modellparameter zeigt einen großen Einfluß der Aggregationsprozesse auf die Subkornmorphologie. Bei niedrigen Monomerumsätzen ist das Zeitintervall zwischen zwei aufeinanderfolgenden Aggregationsschritten sehr klein, so daß für das Teilchenwachstum die Geschwindigkeit der Aggregation der Unterstrukturen entscheidend ist. Im Bereich zwischen 5% und 20% Monomerumsatz sinkt die Aggregationsgeschwindigkeit sehr stark, so daß für das Teilchenwachstum zunehmend die Polymerisationsreaktion an Bedeutung gewinnt. Aggregative Stabilität wird nach dem Modell für einen Teilchengrößenbereich erhalten, der sich in Übereinstimmung mit experimentellen Daten aus der Fachliteratur befindet. Die berechneten Teilchengrößen entsprechen ebenfalls den in der Literatur publizierten experimentellen Werten, so daß das Modell eine gute Grundlage für die Beschreibung einiger morphologisch bestimmter Polymereigenschaften bildet.
    Additional Material: 5 Ill.
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  • 171
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    Angewandte Makromolekulare Chemie 165 (1989), S. 21-34 
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Description / Table of Contents: Es wurden unidirektionale Verbundwerkstoffe aus Novolakharz mit Kohlenstoff-Fasern gemäß der Prepreg-Methode verarbeitet. Das Novolakharz wurde durch Polymerisation von Phenol mit Formaldehyd (Mol-Verhältnis 1 : 0,82) und Oxalsäure als Katalysator (1,5 Gew.-% von Phenol) hergestellt. Die Härtung des Novolakharzes wurde mit Hexamethylentetramin (Hexa) durchgeführt, während das geeignete Verhältnis durch die IR-Spektroskopie bestimmt wurde.Es wurden Proben aus Novolak/Hexa (Gew.-Verhältnis 14: 1), verstärkt mit kommerziellen Kohlenstoff-Fasern, unter verschiedenen Bedingungen (z. B. verschiedene thermische Programme und verschiedene Verhältnisse von Novolakharz : Kohlenstoff-Fasern) hergestellt. Die mechanischen Eigenschaften der hergestellten Proben (wie Biegefestigkeit, Zugfestigkeit, usw.) wurden bestimmt, und ihre Struktur wurde mit Hilfe der Elektronenmikroskopie untersucht.Mit zunehmendem Volumenverhältnis der Kohlenstoff-Fasern werden nicht nur alle mechanischen Eigenschaften des verstärkten Materials verbessert, sondern auch sein Nutzungsgrad nimmt zu, und die Herstellungsbedingungen üben einen größeren Einfluß aus. Die mit dem gleichen Verhältnis von Kohlenstoff-Fasern (z. B. 15 Vol.-%) hergestellten Proben weisen mit zunehmendem Härtungsgrad des Novolaks verbesserte mechanische Eigenschaften auf. Der Häirtungsgrad des Novolaks während der Anfangsphase (Gel-Zeit) als auch während der Endphase (Nachhärtung) kann mit Hilfe der IR-Spektren des härtenden Novolaks verfolgt werden, während der Härtungsgrad der Zwischenphase nur indirekt aus den Werten der mechanischen Eigenschaften der entsprechenden Proben bestimmt werden kann.Aus der Korrelation zwischen den Herstellungsparametern und den mechanischen Eigenschaften der Proben ergeben sich optimale Bedingungen für die Verarbeitung in der Wärmepresse zur Herstellung von mit Kohlenstoff-Fasern verstärkten Novolakharzen (1. Phase: T1 = 125-145°C, t1 = 20 min - 1 h, ohne Druck; 2. Phase: T2 = 180-195°C, t2 = 40 min, P2 ≃ 1,5 kN /cm2).
    Notes: Unidirectional composite materials of novolac resin with carbon fibers were fabricated according to the prepreg method. Novolac resin was prepared by polymerization of phenol with formaldehyde (mole ratio 1 : 0.82) in the presence of oxalic acid as catalyst (1.5 wt.-% to phenol). The curing of novolac resin was performed with hexamethylenetetramine (hexa), while the appropriate proportion was determined by using the IR-spectroscopy.Specimens of novolac/hexa (weight ratio 14:1) reinforced with carbon fibers commercially available were fabricated under different conditions (e.g. different thermal programs and different proportions of novolac/carbon fibers). The mechanical properties of the fabricated specimens (like flexural strength, tensile strength, etc.) were determined and their structure was examined by scanning electron microscopy.By increasing the volume proportion of carbon fibers, not only all mechanical properties of the composite material were increased, but also their degree of utilization was increased and also the production conditions had greater influence. Concerning the specimens produced by the same proportion of carbon fibers (e.g. 15 vol.-%) their mechanical properties were improved by increasing the curing of novolac. The degree of curing of novolac during the initial phase (gel time) and during the ultimate phase (post-curing) can be followed with the aid of IR-spectra of the cured resin, while the degree of curing for the intermediate phase can be obtained only indirectly from the values of the mechanical properties of the corresponding specimens.From the correlation between the production parameters and the mechanical properties of the samples the optimal conditions for processing of the thermopress for the manufacture of carbon fiber reinforced novolac were concluded (1. phase: T1 = 125-145°C, t1 = 20 min - 1 h, without pressure; 2. phase: T2 = 180-195°C, t2 = 40 min, P2 ≃ 1,5 kN/cm2).
    Additional Material: 4 Ill.
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  • 172
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    Angewandte Makromolekulare Chemie 165 (1989), S. 69-78 
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Description / Table of Contents: In dieser Arbeit interessieren wir uns für den Einfluß von Konzentration und Temperatur auf den elektrischen Widerstand eines Butyl-Kautschuks (IIR), der mit zwei Typen von Ruß (Hoch-Abrasion-Schmelzofen-Ruß (HAF) und Schnell-Extrusion-Hochofen-Ruß (FEF)) versetzt ist. Ergebnis war, daß die Leitfähigkeit bei niedrigem Rußgehalt hauptsächlich durch thermische Aktivierung der Ladungsträger erreicht wird. Bei mittleren Konzentrationen überwiegt der Tunnel-Mechanismus bei niedriger Temperatur, gefolgt von der thermischen Aktivierung bei relativ hoher Temperatur. Dies gilt für beide Rußarten. Das metallartige Verhalten bei Gemischen mit hoher Rußkonzentration kann sowohl der thermischen Ausdehnung der Tunnelwege zwischen Kohlenstoff-Agglomeraten als auch dem Zusammenbruch der Kohlenstoff-Agglomerate bei steigender Temperatur zugeschrieben werden.
    Notes: In this study we are interested in the effect of concentration and temperature on the electrical resistivity of butyl rubber (IIR) loaded with two types of carbon black, (namely, high abrasion furnace black (HAF), and fast extrusion furnace black (FEF)). It was found that the conductivity at low carbon black concentrations is mainly achieved by thermal activation of carriers. Tunneling mechanism at low termperature followed by thermal activation at relatively high temperature is found to be predominant for moderate concentrations for both carbon blacks. The metal-like behaviour which was observed in highly loaded compounds was attributed to both, the thermal expansion of the tunneling paths between carbon-carbon agglomerates and the breakdown of carbon agglomerates with temperature.
    Additional Material: 4 Ill.
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  • 173
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    Angewandte Makromolekulare Chemie 165 (1989), S. 79-87 
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Description / Table of Contents: Die Arbeit beschreibt die Synthese von Halogenderivaten des Phenylglycidylethers und die Möglichkeiten der Verwendung von diesen Komponenten als Flammverzögerer und reaktive Verdünnungsmittel für Epoxidharze.Mit Hilfe der Nelder-Mead-Simplexmethode wurden die besten Reaktionsbedingungen gefunden. Die so hergestellten Produkte zeichnen sich durch eine hohe Qualität aus und wurden mit einem niedermolekularen Epoxidharz gemischt und mit Diaminodiphenylmethan gehärtet.Die Viskosität von Harzgemischen und die Brennbarkeit der gehärteten Systeme wurden untersucht. Mit dem erhöhten Gehalt an Halogen (Chlor oder Brom) steigt die Viskosität, und die Brennbarkeit der Epoxide wird reduziert.
    Notes: This study deals with the synthesis of halogenated derivatives of phenyl glycidyl ether and with possibilities of their use as flame retardants and reactive diluents of epoxy resin.The best reaction conditions optimized by Nelder-Mead simplex method were found. The products of very high quality were prepared. They were mixed with a lowmolecular epoxy resin and cured by diamino diphenyl methane.The viscosity of the resin mixtures and limiting oxygen index of cured systems were determined. It was found that a higher content of halogen, both chlorine and bromine, causes increasing viscosity and reduced flammability of the epoxides.
    Additional Material: 2 Ill.
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  • 174
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Description / Table of Contents: Durch Messungen von Tg, Tm und Tc (Trübungspunkt) wurden Phasendiagramme der vier verträglichen Polymermischungen von chlorierten isotaktischen Polypropylenen (Chlorgehalt 39,2 (CPP-40) und 49,8 Gew.-% (CPP-50)) mit Poly(ethylen-co-vinylacetat)en (Vinylacetatgehalt 40 (EVA-40) und 45 Gew.-% (EVA-45)) untersucht. Von den vier Mischungspaaren war die Mischung von CPP-50 mit EVA-40 am besten verträglich.
    Notes: By measuring Tg, Tm and Tc (cloud point) phase diagrams for the four miscible blends of chlorinated isotactic polypropylenes (chlorine content 39.2 (CPP-40) and 49.8 wt.-% (CP-50)) with Poly(ethylene-co-vinyl acetate)s (vinyl acetate contents 40 (EVA-40) and 45 wt.-% (EVA-45)) were investigated. The blend of CPP-50 with EVA-40 was the most compatible of the four blend pairs.
    Additional Material: 4 Ill.
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  • 175
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Description / Table of Contents: Die Synthese und Charakterisierung von Kationenaustauschmembranen aus PE-PS-DVB-Interpolymeren für die Elektrolyse von Borax-Lösung zur Erzeugung von Borsäure und Natronlauge wurden durchgeführt und mit den Eigenschaften von im Handel erhältlichen Membranen („Nafion 324“ und „Permaplex C-20“) verglichen.
    Notes: The synthesis and the characterization of the PE-PS-DVB interpolymer cationexchange membranes in the electrolysis of borax solutions to produce boric acid and sodium hydroxide simultaneously was carried out. The characterization of the teflon based “Nafion 324” and polystyrene-DVB based “Permaplex C-20” membranes was also performed in the same system for comparison.The DVB contents were varied between 3 - 12% (by wt. in total monomers) and the increase of the cross-links resulted in the decrease of the water contents and ionexchange capacities of the membranes. The PE present in the membrane acted as a barrier for electroosmotic water transport. The membranes with high DVB contents showed better electrolysis performance due to their low water contents and low electroosmotic water transport properties. The use of the interpolymer membrane containing 11.6% DVB resulted in high current efficiency and high sodium cation dynamic transport number and worked satisfactorily at the process conditions of borax electrolysis.
    Additional Material: 5 Ill.
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  • 176
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    Angewandte Makromolekulare Chemie 165 (1989), S. 125-131 
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Description / Table of Contents: Aus Rizinusöl und difunktionellen Säuren, wie Oxal-, Malon-, Bernstein-, Glutar-, Adipin-, Suberin- und Sebacinsäure, wurden Prepolyester hergestellt. Diese Prepolyester (PPE) wurden anschließend mit Methylmethacrylat und 1% Ethylenglykoldimethacrylat als Vernetzer interpenetriert. Die Polymerisation wurde radikalisch mit Benzoylperoxid gestartet. Die neuen PPE/Polymethylmethacrylat (PMMA)-interpenetrierenden Netzwerke wurden als Pulver erhalten. Sie wurden durch ihr Löseverhalten, IR-Spektroskopie und ihr thermisches Verhalten charakterisiert.
    Notes: Prepolyesters were obtained from castor oil and dibasic acids, viz oxalic, malonic, succinic, glutaric, adipic, suberic and sebacic acid. These prepolyesters (PPE) were subsequently interpenetrated with methyl methacrylate containing 1% ethylene glycol dimethacrylate as crosslinker by radical polymerization initiated with benzoyl peroxide. The novel PPE poly(methyl methacrylate) PPE/PMMA interpenetrating polymer networks (IPNs) were obtained as powder. They were characterized by solubility behaviour, IR spectral study and thermal behaviour.
    Additional Material: 4 Tab.
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  • 177
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Description / Table of Contents: 2,4-Ionen, ein polymeres quartäres Ammoniumsalz, wurde auf einem makroporösen chlormethylierten Poly(Styrol-co-Divinylbenzol)-Harz (XAD-2) immobilisiert. Der Ionen-Gehalt des Harzes, der durch CHN-Elementaranalyse bestimmt wurde, betrug 50,2 g/kg Harz. Der wichtigste Nebeneffekt des modifizierten Harzes, das Ausbluten des Katalysators 2,4-Ionen, kann durch eine spektrophotometrische Methode, die extrem geringe Konzentraionen an freiem Ionen an der Oberfläche des Harzes messen kann, ermittelt werden.Die Aktivität der immobilisierten 2,4-Ionen/Kobalt(II)-phthalocyanin-tetranatriumsulfonat-Komplexe in bezug auf die oxidative Kupplung von Thiolen ist viel niedriger als im homogenen Fall, aber noch beträchtlich höher als im polymerfreien System. Die beobachtete Abnahme der Reaktionsgeschwindigkeit resultiert nicht aus Behinderungen des Massentransports, sondern vorzugsweise aus den Katalysatoreigenschaften wie z. B. einem sehr niedrigen N+/Co-VerhtUtnis. Die aktiven Zentren scheinen nur in der äußeren Hiille der Harzpartikel vorhanden zu sein.
    Notes: A poly(quaternary ammonium) salt, 2,4-ionene, has been immobilized on a macroporous chloromethylated poly(styrene-divinylbenzene) resin (XAD-2). The ionene content of the resin, determined by CHN elemental analysis, was 50.2 g/kg resin. The most important side effect of the modified resin, catalyst (2,4-ionene) bleeding, can be detected by a spectrophotometric method capable of determining extremely low concentrations of free ionene in the supernatant of the resin.The activity of these immobilized 2,4-ionene/cobalt(II)phthalocyanine-tetrasodiumsulfonate (CoTSPc) complexes towards the oxidative coupling of thiols is much lower than in the homogeneous case, but still considerably higher than for the polymer free system. The observed decrease in reaction rate does not originate from the considerable mass transfer resistances but predominantly from catalyst properties like a very low local N+/Co ratio. The active sites appear to be present in the outer shell of the resin particles only.
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  • 178
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Description / Table of Contents: Röntgendiffraktometrische Untersuchungen und DSC-Messungen an Blend-Filmen, die aus Lösungen von PEEK und PES hergestellt wurden, zeigen eine Phasenseparation bei den Filmen, die bei 340°C hergestellt wurden. Das Kristallisationsverhalten von Filmen, die bei 340°C hergestellt, anschließend abgeschreckt und bei 180°C getempert wurden, ist identisch mit dem von PEEK. Filme, die bei 300°C hergestellt wurden, kristallisierten erst durch Tempern bei 250°C. Blockcopolymere, die aus Oligomeren von PEEK und PES erhalten wurden, unterscheiden sich in dieser Hinsicht von Blends der gleichen Zusammensetzung. Die Glastemperatur von Copolymeren mit einem PEEK-Gehalt von mehr als 50% liegt höher als die von PEEK selbst, während der Schmelzpunkt dieser Copolymeren niedriger als der von PEEK ist.
    Notes: Polymer blends of PEEK with PES were prepared by the solution blending method. Copolymers composed of PEEK and PES components were synthesized from these oligomers. The formation conditions exerted an influence over the molecular aggregation and the crystallization behaviors of the blend films and block copolymers which were examined by X-ray diffractometry and DSC analysis. As a result, phase-separation in the blend films was found when the formation temperature was high. The blend films formed at 340°C, quenched and annealed at 180°C, exhibited the same crystallization behavior as those of PEEK. In the case of the blend films formed at 300°C, the annealing of the films at 250°C was required to crystallize the blend films. The Tg of a copolymer with a PEEK component content of more than 50% tends to shift toward a higher temperature than the Tg of PEEK itself, and the Tm of the copolymer toward a lower temperature than that of PEEK ist.
    Additional Material: 16 Ill.
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  • 179
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    Angewandte Makromolekulare Chemie 168 (1989), S. 129-134 
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Description / Table of Contents: Das Reaktionsprodukt eines Cyclohexanon-Formaldehyd-Harzes mit dem Säurechlorid des Radikalinitiators 4,4′-Azo-bis(4-cyanopentansäure) wurde als Initiator für die Styrolpolymerisation eingesetzt, um ein Cyclohexanon-Formaldehyd-Harz/Polystyrol-Copolymeres zu bilden. Das Copolymere zeigte ähnliche Löslichkeit wie Polystyrol.
    Notes: The reaction product of cyclohexanone-formaldehyde resin with an acid chloride of a radical initiator, 4,4′-azo-bis(4-cyano pentanoic acid) was used as initiator for styrene polymerization to form a cyclohexanone-formaldehyde resin/polystyrene copolymer. The copolymer showed similar solubility as polystyrene.
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  • 180
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    Angewandte Makromolekulare Chemie 168 (1989), S. 145-155 
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Description / Table of Contents: Entgegengesetzte Ladungen wurden durch tertiäre Amin- und Carboxylgruppen in Polyurethan (PU) und Polystyrol (PS) eingeführt, um durch gemeinsame Massepolymerisation ein interpenetrierendes PU/PS Polymernetzwerk (IPN) zu erhalten. Vier IPNs wurden hergestellt: ein Voll-IPN, zwei Semi-IPNs und ein lineares Blend. Die Wirkung der geladenen Gruppen auf die mechanischen Eigenschaften und die Morphologie der vier Polymermischungen wurde untersucht.Es wurde gefunden, daß PU/PS IPNs mit geladenen Gruppen keine Phasenseparation und somit homogene Verteilung aufweisen, was durch elektronenmikroskopische (SEM) Aufnahmen nachgewiesen wurde. Dynamisch-mechanische Messungen zeigen, daß die Übergangspeaks des Verlust-Moduls E″ in die Mitte zwischen den beiden Übergangspeaks der beiden Komponenten ohne geladene Gruppen liegen. Dies ist von der Zunahme des Gehaltes an geladenen Gruppen abhängig. Gleichzeitig nimmt der Speichermodul E′ in einer Stufe ab, was im Gegensatz zu der zweistufigen Abnahme bei Proben ohne Ladungsträger steht.Die Zugfestigkeit nimmt in allen vier Polymermischungen mit der Zunahme an Acrylsäure (AA) in Poly(Styrol-Acrylsäue) PSAA zu, was in dem PU/PSAA Voll-IPN besonders deutlich wird.
    Notes: Opposite charges, namely tertiary amine and carboxyl groups, were introduced into polyurethane (PU) and polystyrene (PS), respectively, to prepare PU/PS interpenetrating polymer networks (IPNs) by means of simultaneous bulk polymerization. Four IPNs were synthesized: a full-IPN, two semi-IPNs and a linear blend. The effect of charge groups on the mechanical properties and morphology of the four polymer alloys was investigated.It is found that the PU/PS IPN which was incorporated with charge groups is free of any phase-separation, and sufficiently uniformly distributed, as can be seen from the corresponding scanning electron microscopy (SEM) photographs. Dynamic mechanical analysis indicates that the transition peak of the loss modulus E″ will move towards the centre between the two transition peaks of both components in the absence of charge groups, as a function of an increase in the contents of the opposite charge groups. Meanwhile the storage modulus E′ will decrease in a single-stage way from the previous two-stage mode.The tensile strength in all the four polymer alloys increased markedly along with an increase in the contents of acrylic acid (AA) in the poly(styrene-acrylic acid) (PSAA), which clearly can be seen for the PU/PSAA full-IPN.
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  • 181
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    Angewandte Makromolekulare Chemie 168 (1989), S. 157-168 
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Description / Table of Contents: Pyrolysis behaviour and coke characteristics of different precursors for carbon processing: thermosetting resins (resol, novolak), hydrolytic lignin, pitch, tar as well as their blends were studied using differential thermal analysis (DTA) and X-ray diffraction techniques. The blends novolak-pitch, resol-tar and resol-hydrolytic lignin show a higher coke yield after carbonisation up to 1000°C compared to the corresponding individual substances. A good correlation between the integral procedural decomposition temperature T*A of the investigated precursors and their coke yield is found.
    Notes: Mittels Thermo- und Röntgenstrukturanalyse wird eine vergleichende Untersuchung des Pyrolysevorganges und der Mikrostruktur des aus zwei Gruppen organischer Bindemittel und deren Mischungen gewonnenen Koksrückstandes durchgeführt. Gruppe I umfaßt reine und mit Hydrolyselignin gefüllte Resol- und Novolak-Phenol-Formaldehydharze und Gruppe II Steinkohlenpech und -teer. Es wird festgestellt, daß sich die Mischungen Novolakharz-Pech, Resolharz-Teer und Resolharz-Hydrolyselignin beim Erhitzen nicht wie mechanische Gemische verhalten und eine erhöhte Ausbeute an Koksrückstand liefern. Weiterhin wird gefunden, daß die integrale Endtemperatur der Pyrolyse (T*A) dieser Substanzen als quantitatives Maß für die Ausbeute an Koksrückstand im Anschluß an die Carbonisierung der Proben dienen kann.
    Additional Material: 4 Ill.
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  • 182
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Angewandte Makromolekulare Chemie 168 (1989), S. 217-223 
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The paper describes the successful synthesis of silicon containing bismaleimide resin 4,4′-carbo(4,4′-bismaleimido phenoxy)diphenyl silane. The char yield of the bismaleimide resin in N2 atmosphere was found to be 55% at 800°C. Chain extension of bismaleimide with 4,4′-diamino diphenyl sulfone reduced the char yield and thermal stability.
    Additional Material: 3 Ill.
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  • 183
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Description / Table of Contents: As hard blocks in polyether block amides, polyamides are used whose length is intensively regulated by dicarboxylic acids. Since, with regard to melting and crystallization behaviour, this acid constitutes an interfering structural unit in the chain, and in the case of a completely converted product each chain contains one acid molecule, it is essential to know where in the chain incorporation will occur. As opposed to monofunctional chain regulators which always form a chain end, a bifunctional chain regulator can a priori also be randomly incorporated into the inner part of the chain. This leads to a far greater interference than occurs if the chain regulator molecule and the chain end, which acts as an interfering unit in any case, coincide with each other.By means of adipic acid-regulated oligoamides based on lauryl lactam, the incorporation of the chain regulator was examined by NMR spectroscopy and compared with model calculations. This resulted in a close match only if it was presupposed that the incorporation was carried out randomly with the same degree of probability at any point whatsoever between two lauryl lactam structural units or at the chain end.Further calculations illustrate the effects of the incorporation of the chain regulator on the size of the amorphous portion.
    Notes: Als Hartblöcke in Polyetherblockamiden werden durch Dicarbonsäuren stark geregelte Polyamide eingesetzt. Da die Säure in Hinblick auf das Schmelz- und Kristallisationsverhalten einen Störbaustein in der Kette darstellt und bei einem ausgeregelten Produkt jede Kette ein Säuremolekül enthält, ist es von Bedeutung zu wissen, wo in der Kette der Einbau erfolgt. Anders als bei monofunktionellen Reglern, wo der Regler stets ein Kettenende bildet, kann ein bifunktioneller Regler a priori auch statistisch im Inneren der Kette eingebaut werden. Dies führt zu einer viel stärkeren Störung, als wenn das Reglermolekül und das sowieso als Störstelle wirkende Kettenende zusammenfallen. Anhand adipinsäuregeregelter Oligoamide auf Basis von Laurinlactam wird kernresonanzspektroskopisch der Einbau des Reglers untersucht und mit Rechnungen verglichen. Es ergibt sich nur dann gute Übereinstimmung, wenn vorausgesetzt wird, daß der Einbau statistisch erfolgt und dabei mit gleicher Wahrscheinlichkeit für jede beliebige Stelle zwischen zwei Laurinlactambausteinen oder am Kettenende abläuft. Weitere Rechnungen verdeutlichen den Einfluß des Reglereinbaus auf die Größe des amorphen Anteils.
    Additional Material: 6 Tab.
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  • 184
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Description / Table of Contents: Auf Grund von mikroskopischen Beobachtungen wurde festgestellt, daß unter dem Einfluß von UV-Strahlung die Oberfläche von PVC-Filmen einer Formveränderung unterliegt. Auf der Oberfläche erscheinen Bläschen und Löcher. Die sich absondernden Gasprodukte der Polymerfotodestruktion verursachen die Bildung dieser Bläschen und Löcher. Größere Oberflächenänderungen wurden in Filmen mit einem Zusatz von 1-5% eines MMA/MA-Copolymeren beobachtet. Das weist auf eine in diesem Modifikator stattfindende Photoabbaureaktion hin, deren Ergiebigkeit größer ist als in reinem PVC. Dieser Modifikator wird in PVC eingeführt, um die Filmoberfläche zu verbessern, beschleunigt allerdings ihre Zerstörung unter dem Einfluß von UV-Strahlung. Es wurde festgestellt, daß Cyclohexanonspuren in den Proben den Photoabbau von MMA/MA retardieren, diesen Prozeß in PVC aber beschleunigen.
    Notes: By means of microscopic observation, the deformation of the surface of PVC films caused by 253.7 nm UV radiation was investigated. Numerous blisters and holes were formed by the gaseous photodecomposition products of the polymer.More apparent deformation of the films containing MMA/MA suggests that the photodecomposition of this modifier occurs with higher efficiency than that of PVC.MMA/MA copolymer is introduced into PVC films to improve the smoothness of their surface, but this modifier accelerates the deformation of this surface under UV irradiation. It was also found that traces of cyclohexanone in samples retard the photodecomposition of MMA/MA and accelerate this process in PVC.
    Additional Material: 7 Ill.
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  • 185
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Angewandte Makromolekulare Chemie 170 (1989), S. 29-41 
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Description / Table of Contents: Eine Anzahl von Harzen wurde durch gemeinsame Kondensation von p-Aminoacetophenon (p-AAph), substituierten Benzoesäuren wie m-Tolylsäure (m-TA), o-Tolylsäure (o-TA), Phthalsäure (PhA), p-Nitrobenzoesäure (p-NBA), p-Chlorbenzoesäure (p-CIBA) und Formaldehyd (F) in Gegenwart von verschiedenen Säuren und Basen als Katalysatoren hergestellt. Die Harze wurden IR-spektroskopisch charakterisiert. Die Löslichkeitsparameter wurden gemäß Small's Gruppenbeteiligung berechnet; sie stimmen gut mit den experimentellen Werten überein. Das thermische Verhalten und die bakteriologischen Eigenschaften der Harze wurden auch untersucht.
    Notes: A number of resins has been prepared by condensing p-amino-acetophenone (p-AAph) with substituted benzoic acid such as m-toluic acid (m-TA), o-toluic acid (o-TA), phthalic acid (PhA), p-nitrobenzoic acid (p-NBA), p-chlorobenzoic acid (p-CIBA) and formaldehyde (F) in presence of some acids and bases as catalysts. The resins were characterized by infrared spectra of the characteristic groups. The solubility parameters were calculated from Small's group contribution which agreed well with the experimental values. The thermal behaviour and the bacteriological properties of the resins have also been investigated.
    Additional Material: 3 Ill.
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  • 186
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Notwithstanding their more common beginnings, liquid crystals and molecular biology developed mainly parallel and independently during the last one hundred years.Molecule-phase relationships on the one and complex static-dynamic treatments on the other hand seem to forward mutually integrative views in our days.Biomesogen approaches will deepen our insights into the spatio-temporal coherences of biological systems. They might contribute significantly to the understanding of life processes.
    Additional Material: 23 Ill.
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  • 187
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Recent studies on ionic distribution in solutions and in suspensions were reviewed. Suspensions of latex particles, which were large enough to be seen under an ultramicroscope, were investigated by the 2-D Fourier transformation. The micrograph showing ordered structures gave discrete scattering spots, whereas those of disordered arrangements displayed no spots or halos. The two-state structure gave a limited number of halo, confirming our previous conclusion that the very frequently observed single, broad scattering peak was reminiscent of some kind of ordering of solute species. By using an image data analyser, the crystallization process was shown to follow the Ostwald ripening mechanism. The concurrent study by the quasi elastic light scattering method and by the Fourier analysis gave consistent scattering profiles, which indicated that the ordering phenomena took place in the entire volume of suspensions. The scattering intensity (correctly the lattice factor) was calculated for cubic systems with paracrystalline distortion. The peak intensity was lowered by enhanced distortion, while the peak position itself was not affected. This justifies our previous treatment of the single, broad peak in terms of the Bragg equation. The experimentally found scattering curve was compared with this theoretical calculation; the degree of distortion was evaluated.
    Additional Material: 14 Ill.
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  • 188
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Lyotropic liquid crystalline phases of cellulose derivatives were explored as an analytical tool. Molar mass dependent measurements of the helicoidal cholesteric pitch of a cellulose tricarbanilate/solvent system may be used to determine the molar mass of this derivative by optical means. The compatibility of a ternary liquid crystalline system can be adequately investigated by a study of the supermolecular structure with spectroscopic measurements.
    Additional Material: 7 Ill.
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  • 189
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The application of carotenoids as natural additives in various water-based or water-compatible formulations for the pigmentation of foods and feeds is seriously hampered by their insolubility in aqueous systems.Therefore, in order to develop the full potential of colour strength and to achieve a high degree of bioavailability during gastro intestinal passage, the coarse crystalline material has to be transformed into a microdisperse state.Exemplified with β-carotene, a novel non-mechanical process is described that transforms the carotenoids into a colloidal hydrosol characterized by an average particle size of about 0.1 μm.The process is based on the preparation of a transient high temperature solute state of the carotenoid in a water-miscible solvent, coupled with succeeding rapid aqueous precipitation in the presence of a stabilizing polymer colloid. The obtained hydrosols are characterized by photon-correlation-spectroscopy(size), and microelectrophoresis(colloidal stabilization).The bioavailability was tested by monitoring plasma levels of β-carotene in veal calves.
    Additional Material: 8 Ill.
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  • 190
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Polymer science is mature enough to allow one to think about tailor-making macromolecular compounds aimed at interacting purposely with living systems. Reasons for developing bioresorbable polymers for temporary therapeutic applications are discussed with respect to property adjustments and economical factors. The field of the applications is first described and guidelines for tailor-making multimeric macromolecules with desired properties are presented. The approach led to focuss investigations on poly(α-hydroxy acids) and functional poly(β-hydroxy acids) derived from natural hydroxy acids, namely lactic, glycolic and malic acids. Physical, mechanical and biological properties of some corresponding polymers and copolymers are presented. Last but not least, examples of applications currently investigated are recalled.
    Additional Material: 1 Ill.
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  • 191
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: When blood comes into contact with an artificial surface, a number of events occur which include protein adsorption, platelet activation and the activation of the intrinsic pathway of blood coagulation. With the increased application of blood containing artificial devices, there is a great demand to develop new biomaterials which retard thrombus formation. Our new approach to solving this problem is to mimic the non-thrombogenic surface of natural biological membranes at least in a simple form. We have developed a polymerisable phospholipid and polyesters based on the major phospholipid polar head group present on the erythrocyte outer membrane surface. The coagulation of blood exposed to these polymers was examined by the technique of Material Thrombelastography, a relatively simple test for the in vitro screening of polymer thrombogenicity. We present results which indicate that the polymerised phospholipid and polyesters show reduced thrombogenicity, and may therefore have potential for future biomaterials.
    Additional Material: 4 Ill.
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  • 192
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: After implantation a stable bond between the implant and the surrounding tissue is required. Therefore a high cell adhesion of the polymer surface of the implant must be achieved. Depending on the treatment time of a polydimethylsiloxane foil with oxygen plasma, the cell adhesion can be improved. FT-IR spectroscopy and ESCA analysis were used to characterize the surface modification. The cell spreading and cell adhesion increase with increasing hydrophilic character of the polymer surface after plasma treatment. A pronounced correlation was found between the efficiency of DNA and protein content, characterizing cell growth, and the spreading of the cells.Polydimethylsiloxane, Glow-Discharge, Surface Modification, Cell Adhesion, Cell Proliferation.
    Additional Material: 6 Ill.
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  • 193
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: We have used synthetic polymers as tools to probe endocytosis and lysosome function. Their particular value lies in their well-defined chemical constitution and in the possibility to custom-synthesize molecules with desired characteristics. Polyvinylpyrrolidone, Percoll and polystyrene beads have been 125I-labelled and used to explore the borderland of pinocytosis and phagocytosis. Derivatized poly(aspartamide), poly(hydroxypropylmethacrylamide) and a polylysine-poly(ethylene oxide) block copolymer have been used to investigate the effects of hydrophobic moieties and sugar residues on substrate-selection in pinocytosis. The effect of cationic moieties has been studied using vinylpyrrolidone-vinylamine copolymers.Poly(hydroxypropylmethacrylamide) with certain oligopeptide side---chains have been shown to be susceptible to lysosomal peptidases. Ethylene glycol oligomers are being used to study the basal permeability of the lysosome membrane.Soluble macromolecules have considerable potential in targeted drug-delivery. Drugs attached to appropriate polymers by covalent links that are susceptible to lysosomal enzymes can deliver drug to target cells and avoid unwanted sideeffects. Synthetic macromolecules have several advantages over their natural counterparts: they are chemically more robust, less immunogenic, and easier and cheaper to prepare in bulk.
    Additional Material: 1 Ill.
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  • 194
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Diagnostics are e. g. reagents or combinations of reagents or measure bloodcomponents down to concentrations of 10-15 mol/1 in reproducable form. To achieve this target diagnostics have to fullfill special requirements in purity, uniformity, producibility and reproducibility. These requirements are also valid for integrated polymers and plastics. Examples of the application of polymers and plastics in diagnostics are e. g. materials for the blood-plasma-separation, the stabilization of proteins, solid phases in immunoassays as reagent tubes, microtiterplates and latexparticles.Reciprocal actions between polymers, plastics, polymer additives, blood and bloodsubstances like proteins in diagnostic tests can be seen as indications to similar effects by the intracorporeal applications of plastics in surgery and in general for contacts of natural materials with plastics, as usual in the foodpacking.
    Additional Material: 19 Ill.
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  • 195
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Using Eupergit, a synthetic resin, as an example, the necessary characteristics of a support for high performance affinity chromatography (HPAC) are demonstrated. To such a support different ligands can be immobilized and used for the separation of biopolymers.From the range of possible applications a few examples are chosen. Immunoglobulins are isolated in one step by protein A-HPAC, the purified antibodies are immobilized and applied to immunoaffinity-HPLC for the isolation of corresponding antigens. Concanavalin A-HPAC of membrane proteins was chosen to represent chromatography with immobilized lectins. Antithrombin could be isolated from human plasma by the use of immobilized heparin. HPAC has the advantage of affinity chromatography, which is above all highly specific. As the support is resistant to high pressure and has well defined microparticles with a particular pore size, it provides a much higher yield at considerable flow rates. The handling of materials like this is simpler, the separation of the sample is quicker and can be reproduced more easily.
    Additional Material: 5 Ill.
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  • 196
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Angewandte Makromolekulare Chemie 166 (1989), S. 257-272 
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Description / Table of Contents: Controlled polyelectrolyte adsorption can be used to render phospholipid bilayer membranes sensitive to physical and chemical signals. We describe in this paper the design and construction of macromolecular switches for bilayer membranes, which can be used to create lipid vesicles that release their contents rapidly and quantitatively in response to changes in pH, temperature, light intensity or glucose concentration. The kinetics and mechanisms of the molecular switching processes observed in such systems are also discussed.
    Notes: Kontrollierte Adsorption von Polyelektrolyten kann ein wirksames Werkzeug im Design von dünnen molekularen Filmen sein. Man kann erwarten, daß die Adsorption von Polyelektrolytketten das empfindliche Kräftegleichgewicht erheblich beeinflußt, das die strukturellen und funktionellen Eigenschaften von geordneten Strukturen wie Einzel-, Doppel- und Mehrfachschichten bestimmt. Andererseits ist die Adsorption von Polyelektrolyten außerordentlich sensitiv auf Umgebungsparameter, z.B. pH, Temperatur oder lonenstärke. Kontrollierte Adsorption kann daher zu Sensitivität auf bestimmte chemische oder physikalische Stimuli führen, sodaß auf diese Weise ein molekularer Schaltmechanismus entworfen werden kann. Durch Umsetzen dieser ldee in reale Systeme gelang es uns, molekulares Schalten in Mischungen von Poly(2-ethylacrylsäre) mit natürlichen oder synthetischen Phosphatidylcholinen zu bewirken. Insbesondere haben wir Phosphatidylcholinvesikel hergestellt, die ihren lnhalt nach einer Änderung von pH, Temperatur, Glukosekonzentration oder nach Bestrahlung mit Licht schnell und quantitativ freisetzen. Die Entwicklung und die Herstellung von Doppelschichtmembranen, die auf solche Änderungen reagieren, sowie die Kinetik und der Mechanismus des damit verbundenen molekularen Schaltprozesses werden im vorliegenden Artikel diskutiert.
    Additional Material: 9 Ill.
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  • 197
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Enzymes can be immobilized by gel entrapment, by microencapsulation, by physical or ionic adsorption, by covalent binding to inorganic or organic carriers, or by whole cell immobilization. Of particular interest is the large number of chemical reactions developed for the covalent binding of enzymes via their nonessential functional groups to inorganic carriers such as glass, ceramics and iron, to natural polymers such as cellulose and Sepharose, and to synthetic polymers such as nylon, polyacrylamide, and other vinyl polymers and copolymers possessing reactive chemical groups. The stability of certain enzymes is markedly increased on their immobilization. It was thus possible to transform the biologically active polymer derivatives into active enzyme beads, enzyme capsules, enzyme columns and enzyme membranes and these enabled the construction of enzyme reactors such as the batch-stirred tank reactors, the continuous packed bed reactors, and fluidized bed reactors. So far mainly immobilized hydralases and isomerases are being used in industry on a large scale. It seems likely, however, that once adequate techniques become available for cofactor recycling, the use of immobilized enzymes will be extended to other organic reactions, particularly those involving stereospecific synthesis of simple or complex organic molecules. Among the industrial processes in which immobilized enzymes are being used, it is worth mentioning the industrial-scale continuous production of fructose enriched syrup from glucose by immobilized glucose-isomerase, the batch process for the production of 6-aminopenicillanic acid (6-APA) from penicillin G with the aid of immobilized penicillin amidase; the production of aspartame from aspartic acid and phenylalanine by immobilized thermoase; the large scale production of optically active amino acids with immobilized amino acid acylase; and the large scale production and application of immobilized lactase for the hydrolysis of lactose. The recently developed process for acrylamide production using immobilized nitrilase containing microbial cells should also be referred to. The successful use of an NAD-polyethylene glycol conjugate (NAD-PEG) as a nondialyzable water-soluble coenzyme derivative in the enzymic synthesis of leucine from α-ketoisocaproic acid and ammonia, in a membrane-enclosed reactor containing L-leucine dehydrogenase, NAD-PEG, formate and formate dehydrogenase, illustrates the new possibilities opened up by making use of cofactor-polymer conjugates. The use of enzyme-polymer conjugates in analytical and clinical is also illustrated.
    Additional Material: 5 Ill.
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  • 198
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The genetic make-up of living systems especially of isolated cells can be altered by a variety of methods including chemical or light-induced mutation. More modern procedures are the in vitro recombination of nucleic acids and the cell-cell fusion.The new methods are especially useful to reprogram microorganisms to produce valuable proteins or other natural products in excess quantties. In the following we will elucidate the importance of the new techniques by describing the bacterial production of glucose dehydrogenase, of the proteinase inhibitor stefin A and by outlining the methods and promisses of substractive cloning. Although the economic value of genetic engineering techniques still awaits justification, the importance of the methodology for basic biological research is well documented.
    Additional Material: 12 Ill.
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  • 199
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Immobilization of whole cells has become an efficient tool for biosynthesis, biotransformation and analysis. High cell density, high operational stability, easy handling, propably in continuous systems, and multiple reuse are important advantages of immobilized cells. In comparison to other methods like adsorption, crosslinking and encapsulation, the entrapment within a polymeric network is the most widely applied technique in heterogeneous biocatalysis. For immobilizing mammalian cells nearly exclusively the adsorption onto micorcarriers is used. Requirements for the polymers to be used in such immobilized cell systems are discussed in detail.
    Additional Material: 5 Ill.
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  • 200
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Angewandte Makromolekulare Chemie 168 (1989), S. 1-8 
    ISSN: 0003-3146
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Description / Table of Contents: Vier Pyridazinderivate wurden synthetisiert und als Beschleuniger für Naturkautschukmischungen entwickelt. Die rheologischen Eigenschaften wurden mit Hilfe eines Monsanto Rheometers 100 bestimmt. Die rheometrischen Daten wurden für die Berechnung der kinetischen Konstanten der Vulkanisationsreaktion in Anwesenheit der synthetisierten Verbindungen benutzt. Verglichen mit Mercaptobenzthiazol (MBT), einem Beschleuniger der häufig in der Kautschukindustrie eingesetzt wird, zeigten diese Verbindungen eine gute Beschleunigerwirksamkeit.
    Notes: Four pyridazine derivatives were synthesized and evaluated as accelerators in natural rubber (NR) mixes. The rheological characteristics were determined by a Monsanto Rheometer 100. The kinetic constants for the vulcanization reaction in the presence of the synthetic compounds were calculated using the rheometric data. The compounds showed a good accelerating efficiency compared with mercaptobenzothiazole (MBT), which is widely used in rubber industry.
    Additional Material: 1 Ill.
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