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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 385-391 
    ISSN: 1432-1041
    Schlagwort(e): sulpiride ; pharmacokinetics ; serum clearance ; renal clearance ; bioavailability ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of sulpiride was studied in 6 healthy volunteers after intravenous and oral (tablets) administration of 100 mg. An open two- and in two subjects a three-compartment model was applied following intravenous administration. The average total distribution volume during the terminal slope was 2.72±0.66 l/kg and total systemic clearance was 415±84 ml/min. The serum half-life of the terminal slope following intravenous administration averaged 5.3 h (range 3.7–7.1 h) according to the two-compartment model. In two subjects the half-lives were 11.0 and 13.9 h when the three-compartment model was applied. Determination of urinary excretion rates of unchanged sulpiride indicated a half-life of 7.15 h. Following intravenous administration, 70±9% of the dose was recovered unchanged in urine within 36 h; the mean renal clearance was 310±91 ml/min. Sulpiride was absorbed slowly, with peak concentrations appearing between 3 and 6 h after oral administration. The recovery of unchanged drug in urine following oral administration was 15±5% of the dose, with a mean renal clearance of 223±47 ml/min. The bioavailability determined from combined plasma and urine data was only 27±9%. The low bioavailability was probably due to incomplete absorption.
    Materialart: Digitale Medien
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 22 (1982), S. 175-179 
    ISSN: 1432-1041
    Schlagwort(e): pethidine ; norpethidine ; analgesic ; singledose kinetics ; plasma concentrations ; drug disposition ; geriatric patients
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Pethidine was given as a single intravenous dose for premedication before minor surgery. Two groups of subjects were studied, old patients aged more than 65 years, and young patients aged 18–30 years. Blood samples were taken at fixed intervals for 30 h after the injection, and the plasma concentrations of pethidine and its major metabolite norpethidine were analyzed by gas chromatography. In comparison with the young the old patients had a lower plasma clearance for pethidine (9.13±2.50 versus 16.18±5.15 ml/min/kg), slower elimination rate β (0.101±0.036 versus 0.211±0.146), and a larger AUC (1935±554 versus 1092±277 h · ng/ml) but a similar volume of distribution (5.69±1.54 versus 5.38±1.75 l/kg). Norpethidine appeared later and reached its peak concentration later in the old patients than in the young. In several old patients it was still present at a plateau level after 30 h. The present study emphasizes that both parent drug and active metabolite must be taken into consideration when drug therapy is evaluated. The data do not provide pharmacokinetic support for a reduction in the dose of pethidine if it is given as a single intravenous dose. However, when repeatedly administered, it is advisable to reduce the total daily dose.
    Materialart: Digitale Medien
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 23 (1982), S. 457-461 
    ISSN: 1432-1041
    Schlagwort(e): geriatrics ; pethidine ; drug disposition in blood ; erythrocytes ; age effect ; plasma protein binding ; red cell binding ; intracellular concentration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The distribution of3H-pethidine in whole blood was compared in old (63–86 years;n=11) and young (19–25 years,n=12) subjects using equilibrium dialysis. The plasma protein binding was 52.7±3.3% (mean ± SD) in the old subjects and 51.8±3.1% in the young; the difference was not statistically significant. Studies on isolated plasma protein fractions showed that the main pethidine-binding protein wasα 1-acid glycoprotein. Accordingly, the degree of pethidine binding is likely to be affected by inflammatory disease rather than by age. The distribution of pethidine to blood cells showed no age-related difference; the ratio between whole blood and plasma concentrations was 0.99 in old and 0.98 in young subjects. In whole blood from old and young subjects, 43% and 41% of pethidine was present in erythrocytes, 27% and 26% in plasma water whereas 30% and 29% was bound to plasma proteins. The mean ratio between pethidine in cells and plasma water (2.01) indicates binding of the drug in or on the blood cells. These in vitro results do not support the previous theory that a decrease in intracellular pethidine distribution in old age was the reason for the reported higher plasma levels. A slower elimination rate remains the most likely explanation for the increased plasma concentration of pethidine in old patients.
    Materialart: Digitale Medien
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 27 (1985), S. 713-719 
    ISSN: 1432-1041
    Schlagwort(e): flucloxacillin ; cardiac pacemaker ; pharmacokinetics ; protein binding ; tissue fluid ; elderly patients
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of flucloxacillin in plasma and tissue fluid after i.v. infusion of 1 g was analyzed according to an open two-compartment model in 19 patients with bradyarrhythmias (mean age 70.8 years) admitted for implantation or replacement of a permanent pacemaker system. After the first infusion of flucloxacillin (5 min), the distribution phase was rapid (t1/2α=0.13 h). The plasma half-life of elimination (t1/2β) was 1.51 h, which is almost twice as long as reported in healthy volunteers. Total plasma clearance (93.1 ml/min) was also lower than is usually found in healthy individuals, due to low renal clearance of flucloxacillin (60.2 ml/min). The total apparent volume of distribution during the β-phase (Vdarea) was 0.172 l/kg and distribution in the central compartment (Vc) 0.064 l/kg. In each patient plasma protein binding and drug distribution to plasma water, proteins and blood cells in whole blood were determined. Binding in plasma to proteins was 91.0% and distribution to blood cells in whole blood 13.8%. The mean distribution volume of free flucloxacillin during the β-phase (Vdβ free) was 2.18 l/kg, which exceeds total body water, suggesting possible intracellular distribution and substantial tissue binding. Plasma concentrations of flucloxacillin after the fourth dose (1 g t.i.d.) were very similar to those obtained after the first infusion and those predicted from the single dose kinetics. The concentration of flucloxacillin in fluid from the pacemaker pockets in 5 patients averaged 12.1 µg/ml and 9.5 µg/ml at 1 and 5 h, respectively, which was more than ten times the MIC-values for Staphylococcus aureus and S. epidermidis. The average concentration ratio (tissue fluid/plasma) was 0.57. Thus the pharmacokinetics of flucloxacillin in these elderly patients exhibited marked differences from what has been found in healthy volunteers. Despite the high degree of plasma protein binding, flucloxacillin appears to distribute rapidly and efficiently to extravascular compartments, such as a pacemaker pocket.
    Materialart: Digitale Medien
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 16 (1979), S. 211-215 
    ISSN: 1432-1041
    Schlagwort(e): fluoride ; bioavailability ; calcium
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of milk products on the gastrointestinal absorption of fluoride from sodium fluoride tablets was studied in five healthy subjects. Two different diets were tested: (1) 250 ml standardized milk (3% fat) and (2) 500 ml of milk, 3 pieces of white bread with cheese and 150 ml of yoghurt. The 100% bioavailability of sodium fluoride tablets during fasting was greatly decreased by coadministration of milk products: with Diet 1 the absolute bioavailability calculated from combined plasma and urine data was in the range 50–79% and with Diet 2 it ranged from 50–71%. It is suggested that the decreased bioavailability produced by dairy products should be taken into account when establishing fluoride dosage regimens for prophylaxis of caries.
    Materialart: Digitale Medien
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 189-194 
    ISSN: 1432-1041
    Schlagwort(e): fluoride ; renal clearance ; urinary pH ; fluoride kinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Five healthy subjects were each given fluoride 3.0 mg (F) as sodium fluoride tablets on two occasions — during production of acid urine, induced by giving NH4Cl, and during production of alkaline urine obtained by giving NaHCO3. Frequent plasma and urine samples were taken up to 12 h and were analyzed with a F− sensitive electrode. Control experiments without F administrations were also performed to permit calculation of net F concentration in plasma and urine. The urine F excretion was lower during acid than alkaline diuresis. Pharmacokinetic analysis of the net plasma F concentrations showed that the apparent plasma half-life of F was longer when urine was acid (4.3±0.6 h: SD; n=5) than when it was alkaline (2.4±0.4 h). This could be explained by changes in the renal clearance of F, which was always lower with an acid (61.5±8.1 ml/min) than an alkaline (97.8±10.4 ml/min) urine. The apparent extra-renal clearance, which mainly represents clearance to the bone-pool, was also significantly higher during production of alkaline (109.2±20.2 ml/min) than of acid (86.3±21.3 ml/min) urine. It is suggested, that increased reabsorption of non-ionic hydrogen fluoride (HF) is responsible for the decreased renal clearance during acidic conditions.
    Materialart: Digitale Medien
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  • 7
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 22 (1982), S. 351-358 
    ISSN: 1432-1041
    Schlagwort(e): cloxacillin ; flucloxallin ; maternal — fetal distribution ; whole blood levels ; erythrocyte content ; plasma binding ; bilirubin effect
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The distribution of cloxacillin and flucloxacillin in whole blood from seven newborn infants and their mothers was determined in vitro by equilibrium dialysis at 37°C. Seven healthy, non-pregnant women of reproductive age served as controls. The distribution of the penicillins to erythrocytes was the same in the infants as in the adults. It was significantly lower in the presence of plasma albumin than when plasma was replaced by isotonic phosphate buffer. The plasma protein binding of cloxacillin and flucloxacillin in 22 infants was significantly lower than in the controls, but was slightly higher than in the mothers. A significant correlation between binding of cloxacillin and flucloxacillin in the same individual suggested that the two drugs were bound to similar sites. During the first postnatal week binding in infant plasma decreased. This change was correlated with an increase in the bilirubin levels. In the mothers, the binding increased during the first week after delivery. On the basis of the distribution data, maternal to fetal plasma and whole blood concentration ratios at equilibrium were calculated. These ratios were lower for flucloxacillin (medians 0.770 and 0.821, respectively) than for cloxacillin 0.996 and 1.094). Accordingly, at equilibrium somewhat higher levels of flucloxacillin should appear on the fetal than on the maternal side, whereas the concentrations of cloxacillin would be expected to be approximately the same.
    Materialart: Digitale Medien
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 11 (1977), S. 37-42 
    ISSN: 1432-1041
    Schlagwort(e): Pentobarbital ; diphenylhydantoin ; salicyclic acid ; protein binding ; erythrocytes ; cell equilibration ; temperature effect
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The binding of pentobarbital, diphenylhydantoin and salicylic acid to cells in blood was found to be independent of total drug concentration within therapeutic levels. Salicylic acid displaced pentobarbital and diphenylhydantoin from plasma protein binding sites, but high levels of salicylic acid had no effect on the distribution of the other two drugs to washed blood cells. Thus, in whole blood the presence of salicylic acid decreased the fraction of pentobarbital or diphenylhydantoin bound to plasma protiens and increased the fraction of the drug in plasma water and in blood cells. Diphenylhydantoin was shown not to be bound irreversibly to blood cells and equilibration in between the inside and outside of the cells was found to be rapid (within 5 min), even at high concentrations. Binding to washed blood cells was the same at 37°C and 25°C, in contrast to plasma protein binding. It is pointed out that these effects may cause certain analytical errors, resulting in changes in plasma concentration if plasma is separated at a low temperature.
    Materialart: Digitale Medien
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  • 9
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 4 (1972), S. 191-195 
    ISSN: 1432-1041
    Schlagwort(e): Amobarbital ; pentobarbital ; barbiturates ; gas chromatography ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Gas chromatographic methods are described for the assay of amobarbital and pentobarbital in 500 µl samples of plasma, in concentrations down to 250 ng/ml. After ether extraction at pH 5.5, the barbiturates are reextracted into an alkaline solution of trimethylanilinium hydroxide and are determined quantitatively by gas chromatography as their dimethylated derivatives. The method has been used successfully in volunteers receiving therapeutic doses of these bariturates.
    Materialart: Digitale Medien
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  • 10
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 403-409 
    ISSN: 1432-1041
    Schlagwort(e): flucloxacillin ; newborn infants ; bioavailability ; plasma protein binding ; side-effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Flucloxacillin 50 mg/kg b.w. was administered intravenously (in combination with ampicillin/gentamicin) and orally (with amoxicillin) to 9 newborn infants (gestational age 33–41 weeks) to treat bacterial infections. The concentrations of flucloxaxillin in plasma and urine after i.v. injection were analysed according to an open two-compartment model, and the plasma protein binding of flucloxacillin and its distribution to blood cells and plasma water in whole blood were determined. Considerable differences were found from values reported in adults. The terminal half-life averaged 4 h 38 min and was significantly correlated with gestational age. Plasma clearance was low (0.744 ml·min−1·kg−1), due to the small renal clearance (0.182 ml·min−1·kg−1), whilst non-renal clearance (0.563 ml·min−1·kg−1) was approximately the same as in adults. The mean apparent volume of distribution of total drug (Vz) was 0.280 l/kg. The corresponding volume of distribution of unbound drug (V 1 u + V 2 u ) was 1.74 l/kg, which indicates considerable extravascular drug binding. The plasma protein binding of flucloxacillin (mean 86.3%) was significantly correlated with gestational age and the bilirubin/albumin concentration ratio. Bioavailability after oral administration, when corrected for changes in terminal half-life, was 47.7%, which is only slightly lower than that reported in adults. Since the plasma concentrations after both i.v. and oral administration were well above the MIC-values generally reported for Staphylococcus aureus, and since few side-effects were observed, intravenous injection or, in selected cases, oral administration of flucloxacillin appears to be a reliable therapy for the treatment of infections due to sensitive strains of S. aureus in premature newborn infants.
    Materialart: Digitale Medien
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