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  • 1
    Electronic Resource
    Electronic Resource
    Chronobiological studies on the blood-brain barrier (1981)
    Springer
    Cellular and molecular life sciences 37 (1981), S. 1013-1015 
    Details
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Horseradish peroxidase (HRP) is a useful tracer for a study of the transportation of exogenous materials across vascular walls. After i.v. administration of HRP, reaction products of HRP can be recognized in the granular perithelial cells of small cerebral blood vessels at particular times of day. It suggests that there is a time-dependent fluctuation in the permeability of small cerebral blood vessels.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01971811
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  • 2
    Electronic Resource
    Electronic Resource
    Antipyrine clearance in patients with Gilbert's syndrome (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 297-302 
    Details
    ISSN: 1432-1041
    Keywords: Gilbert's syndrome ; antipyrine clearance ; drug oxidizing capacity ; smoking habit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic parameters of antipyrine (AP) were examined in 45 normal healthy subjects (18 heavy smokers, 5 mild smokers, and 22 nonsmokers) and in 12 patients with Gilbert's syndrome (GS), amongst whom 2 mild and 1 heavy smokers were included. Heavy smokers were defined as persons smoking more than 20 cigarettes/day and mild smokers as those smoking less than 10 cigarettes/day. Significant differences (unpaired Student's t-test) in the elimination t1/2 of AP among the study groups and in its total plasma clearance (CL) were observed without any change in the apparent volume of distribution. The individual CL values varied within the same study groups, but the mean±SD (0.026±0.004 l/h/kg) in the GS patients did not significantly differ from that in normal nonsmokers (0.025±0.006 l/h/kg) or in normal mild smokers (0.028±0.001 l/h/kg). When the 3 patients with GS who smoked were excluded, the mean CL of the group (0.025 l/h/kg) was again comparable to that of the normal nonsmokers and mild smokers. The mean (±SD) CL in normal heavy smokers (0.040±0.012 l/h/kg) was significantly greater than in normal mild smokers (p〈0.05), in normal nonsmokers (p〈0.001) and in patients with GS (p〈0.001). The results suggest that drug oxidation capacity estimated from the total plasma CL of AP appears unimpaired in GS.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542163
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  • 3
    Electronic Resource
    Electronic Resource
    Serum doxapram and respiratory neuromuscular drive in normal man (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 55-59 
    Details
    ISSN: 1432-1041
    Keywords: doxapram ; ventilatory function ; occlusion pressure ; serum drug concentration ; concentration-effect relationship
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To investigate the means by which doxapram affects the control of ventilation, ventilatory function and P0.1 have been related to serum doxapram concentration during a 45-min infusion of doxapram hydrochloride in 7 healthy, conscious subjects under normoxic conditions. Serum doxapram concentrations increased during the infusion: 1.88, 2.48, 3.42, and 3.97 µg/ml after 5, 10, 30 and 45 min, respectively. The majority of significant changes in the measurements from the baseline were observed at 30 and 45 min: $${{\dot V}}_{{E}}$$ , VT, P0.1, P0.1/end-tidal CO2 tension, VT/Ti and blood pressure were increased, and end-tidal CO2 tension was decreased. No significant changes in Pdimax, Ti/Ttot, $${{\dot V}}_{{E}}$$ /P0.1, and P0.1/(VT/Ti) were observed. A correlation was observed between the % increases in P0.1 and $${{\dot V}}_{{E}}$$ and doxapram concentration, and between $${{\dot V}}_{{E}}$$ and P0.1. The doxapram-induced increase in $${{\dot V}}_{{E}}$$ appears to be caused by increased neural drive. It is related to the serum drug concentration in the conscious subject.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01061418
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  • 4
    Electronic Resource
    Electronic Resource
    Effect of theophylline on respiratory neuromuscular drive (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 85-88 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; aminophylline ; incremental concentration ; occlusion pressure ; maximum inspiratory pressure ; transdiaphragmatic pressure ; ventilatory function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To investigate the possible mechanisms by which theophylline affects the control of ventilation, neuromuscular drive and ventilatory function were examined in 7 healthy men receiving an incremental intravenous aminophylline dosing schedule to achieve plasma theophylline concentrations of 5, 10, and 15 µg/ml. As compared with the baseline (predose) values, the 3 incremental aminophylline doses significantly (p〈0.05 to 0.01) increased occlusion pressure (P0.1) and maximum inspiratory pressure static (MIPS) at functional residual capacity (FRC). This was not observed for ventilatory flow $$(\dot V)$$ , tidal volume (VT), inspiratory time to total breathing cycle time ratio (Ti/Ttot), VT/Ti, and effective impedance [P0.1/(VT/Ti)]. When maximum electrical activity of diaphragm (Edimax) and transdiaphragmatic pressure (Pdimax) were examined in 3 of the 7 subjects, Pdi/Edi tended to increase with increasing theophylline concentrations, while Edimax did not. Our results suggest that the increase in P0.1 during the increase in aminophylline dose is caused by an improvement in respiratory muscle contractility, rather than by a central effect or by an increase in neural drive.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00610386
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  • 5
    Electronic Resource
    Electronic Resource
    Genetically determined N-acetylation and oxidation capacities in Japanese patients with non-occupational urinary bladder cancer (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 581-587 
    Details
    ISSN: 1432-1041
    Keywords: metoprolol ; dapsone ; bladder cancer ; acetylator phenotype ; oxidative phenotype ; pharmacogenetics ; Japanese
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Genetically determined polymorphisms of N-acetylation and oxidative capacity have been studied using dapsone and metoprolol in 51 Japanese patients with spontaneous bladder cancer and 203 healthy control subjects. The results for N-acetylation pharmacogenetics were against the initial expectation that there would be a preponderance of slow acetylators in the cancer group, as 3 such patients (5.9%) were found as compared to 13 (6.4%) in the healthy group. There was no poor metabolizer (PM) of metoprolol in the cancer group, whereas in the healthy group one (0.5%) was a PM. There were no significant differences between the groups in the frequency of slow acetylator and poor oxidiser phenotypes, or in the frequency distribution profiles of acetylation (monoacetyldapsone/dapsone) and oxidative metabolic ratio (log metoprolol/α-hydroxymetoprolol). The results indicate that neither N-acetylation nor the debrisoquine/sparteine-type oxidative phenotype and/or capacity represent a genetic predisposition to spontaneous bladder carcinogenesis in Japanese patients. In the normal Japanese population there is a great predominance of rapid acetylators and extensive oxidisers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562549
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  • 6
    Electronic Resource
    Electronic Resource
    Acute effect of an alpha1-adrenoceptor antagonist on urinary sodium excretion, plasma atrial natriuretic peptide, arginine vasopressin, and the renin-aldosterone system in healthy subjects (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 17-21 
    Details
    ISSN: 1432-1041
    Keywords: Alpha1-adrenoceptor antagonist ; Bunazosin ; Sodium retention ; atria ; natriuretic peptide ; arginine vasopressin ; renin-aldosterone system ; enalapril ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To elucidate the mechanism underlying the sodium retention caused byα 1-adrenoceptor blockade in man, a placebo-controlled, randomised, double-blind study has been made of the acute effects of bunazosin anα 1-antagonist, on urinary sodium excretion, atrial natriuretic peptide (ANP), arginine vasopressin (AVP), and the renin-aldosterone system in 7 healthy men. A single oral dose of bunazosin 2.0 mg caused a significant reduction (P 〈 0.05) in urinary sodium excretion after 0–2 h, 2–4 h, and 4–6 h. The mean values for plasma ANP, AVP, aldosterone, and cortisol concentrations at those times were similar after placebo and bunazosin, and plasma renin activity was significantly increased 2 and 4 h after bunazosin. Pretreatment with oral enalapril 10 mg, an angiotensin converting enzyme inhibitor, did not prevent the bunazosin-induced reduction in urinary sodium excretion. There was a significant positive correlation between the drug-induced changes in blood pressure and urinary sodium excretion. The results suggest that ANP, AVP, and renin-aldosterone may play little role in the sodium retention caused by acuteα 1-adrenoceptor blockade in man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02280748
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  • 7
    Electronic Resource
    Electronic Resource
    Comparison of disposition and effect of timolol and propranolol on exercise tachycardia (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 7-14 
    Details
    ISSN: 1432-1041
    Keywords: Timolol ; propranolol ; disposition ; plasma level ; beta-blockade assessment ; duration-action course of drug
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetic disposition and beta-adrenergic blocking action in relation to plasma level of a single oral dose of either timolol or propranolol has been compared in healthy male volunteers. The disposition profiles clearly disclosed different properties of the two drugs, although their half-lives were similar. The available fraction of timolol in the systemic circulation was estimated to be approximately 60% of the dose, and 17.4% was exereted unchanged in urine. The logarithm of plasma concentration showed a significant correlation with the beta-blocking activity assessed by an exercise test. The mean potency ratios of timolol to propranolol as an antagonist of chronotropic effects on exercise tachycardia were 11 to 17 and 3.6 to 5.5 in dose- and concentration-effect relationships, respectively. The absolute reduction of exercise heart rate gave the best coefficient of all measures of beta-blockade. When drug action was measured as beta-blockade assessed by a given response to exercise tachycardia, the effect declined linearly with time, even though plasma levels fell exponentially. This results suggest that the pharmacokinetic t1/2 is much shorter than the pharmacological t1/2.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00560252
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  • 8
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of ketoprofen following single oral, intramuscular and rectal doses and after repeated oral administration (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 407-414 
    Details
    ISSN: 1432-1041
    Keywords: ketoprofen ; pharmacokinetics ; relative bioavailability ; single doses ; repeated doses ; prediction of kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of ketoprofen was studied in the same healthy subjects after single oral, intramuscular and rectal doses, and after repeated oral administration. No significant difference in the mean t1/2 (1.13–1.27 h) was observed after the different modes of administration. The mean [AUC] 0 ∞ after rectal administration of a suppository showed the minimum significant difference (p〈0.05) from that after oral administration of the capsule. The apparent volume of distribution (Vd/F) was approximately 10–15% of body weight. The renal contribution (mean, 0.10–0.15 ml/min/kg) to the plasma clearance of free ketoprofen was assumed to be, at most, 8.3–12.9%. The projected cumulative excretion of total (free plus conjugated) ketoprofen via urine exceeded 63–75% of the dose, of which approximately 90% was ketoprofen glucuronide. A mean of 71–96% and 73–93% of the oral capsule was estimated to be systemically available after administration of the intramuscular preparation and rectal suppository, respectively. In four of seven subjects, CPK concentration was elevated after the intramuscular injection. The mean steady-state concentration of ketoprofen in plasma ranged from 0.43 to 5.62 µg/ml after the final dose of a 50 mg q.i.d. regimen. The disposition data and plasma levels observed at steady-state were in agreement with those predicted from the single oral dose study. The accumulation ratio was 1.08±0.08. The results suggest that the rectal suppository can be recommended as an extravascular mode of administration of this drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00636794
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  • 9
    Electronic Resource
    Electronic Resource
    Bioavailability and pharmacokinetics of theophylline following plain uncoated and sustained-release dosage forms in relation to smoking habit (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 361-369 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; smoking ; sustained release formulation ; dosage forms ; multidose pharmacokinetics ; bioavailability ; circadian variation in kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and bioavailability of theophylline following 10 days of multiple doses of a plain uncoated (640 mg, q.i.d.) and a sustained-release tablet formulation (600 mg, b.i.d.) were related to habitual smoking in 11 healthy adult male volunteers, who had previously taken part in a single-dose study of an intravenous preparation of theophylline and of the same oral dosage form. There were significant differences (p〈0.05 to 0.01) in the steady-state mean and minimum theophylline concentration and AUC between the groups (6 smokers versus 5 nonsmokers), but not between other variables. A difference (p〈0.05) in peak time was also found between the dosage forms. The mean elimination t1/2 was significantly (p〈0.05) shorter in smokers than in nonsmokers. The intersubject variability in plasma theophylline concentration observed on the final trial day in the smoking group was larger and diverged more from simulation curves generated from the mean pharmacokinetic parameters of the single-dose study of the same formulations as compared to that of the nonsmoking group. There was no significant difference between the two groups in the mean accumulation ratio and absolute bioavailability of the two dosage forms. The mean morning (7 a.m.) trough theophylline concentrations after both formulations were significantly (p〈0.05 to 0.01) greater than the evening (7 p.m.) values within the same group. The average number of reported side-effects was significantly (p〈0.001) greater during the earlier period (Days 1 to 3) than the later period of the trial. A trend was observed suggesting that the incidence of side-effects was less in smokers than in nonsmokers. The results indicate that smoking is a determinant not only of enhanced elimination of theophylline but that it also produces more variability in the plasma level, irrespective of the dosage form administered or the dosing scheme employed. There may be circadian variation in theophylline kinetics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00610056
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  • 10
    Electronic Resource
    Electronic Resource
    Bioavailability and pharmacokinetics of theophylline in plain uncoated and sustained-release dosage forms in relation to smoking habit I. Single dose study (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 79-87 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; smoking habit ; absolute bioavailability ; pharmacokinetics ; sustained release preparation ; plain tablet preparation ; antipyrine pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability and pharmacokinetics of theophylline from a plain uncoated and 2 newly designed, sustained-release tablet formulations, as compared to intravenous aminophylline, were studied in 12 healthy adult male volunteers. The subjects were divided into two groups (n=6) with respect to smoking habit and on 4 separate occasions each received, on a randomized cross-over basis, a single dose of 400 mg equivalent of theophylline from every dosage form. The intravenous aminophylline study showed that habitual smoking had a significant (p〈0.05) effect on plasma theophylline clearance (0.051±0.006 vs 0.035±0.004 l/kg/h). Smoking significantly reduced the raw AUC from the 4 dosage forms (p〈0.05), but did not change the characteristics of absorption of each formulation. There was a non-significant trend towards reduced absolute bioavailability of theophylline from sustained-release formulations in smokers (percentage mean difference — 16% for one formulation and 13% for another). The trend was not observed for the plain uncoated tablet, which was rapidly absorbed (p〈0.01 to 0.05 in Ka, tmax and Cmax compared to sustained-release tablets). Similarity of the in vitro dissolution profiles of the two sustained-release formulations did not imply similarity of the in vivo absorption characteristics. Plasma clearances of theophylline and antipyrine were significantly correlated (p〈0.05,r=0.693,n=10). Thus, smoking enhanced the elimination of theophylline regardless of the dosage form administered. However, the extent to which habitual smoking may affect the hepatic first-pass effect on theophylline from sustained-release formulations requires further study. The results also suggest that theophylline and antipyrine may share a similar or common and presumably polycyclic hydrocarbon-inducible form(s) of microsomal drugmetabolizing enzyme.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613931
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