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Biomedical subjects

P B Zuiderwijk

Publications and source records attributed to P B Zuiderwijk.

7 recordsLinked to original sources
PubMed1996

Lack of interaction between orlistat and oral contraceptives.

OBJECTIVES: Orlistat, a potent and selective inhibitor of gastrointestinal lipases, is designed for the treatment of obesity. A double-blind, randomised, placebo-controlled, 2-way crossover study investigated the possible influence of orlistat on the ovulation-suppressing action of combination oral contraceptives (OC). METHODS: After an 8-day run-in prior to the first of two consecutive menstrual cycles (Day 1 was the first day of menstruation), two groups of 10 healthy women, 20-27 years of age and on a stable regimen with OCs, received either 120 mg orlistat t.i.d. or placebo t.i.d. on Days 1-23 of the first cycle, and, separated by a placebo washout period on Days 24-28, the alternative treatment on Days 1-23 of the second cycle. In both cycles, serum luteinizing hormone (LH) was measured on Days 12-16 and progesterone on Days 12, 16, 19-23. RESULTS: The geometric means of time averaged concentrations (Days 12-16 for LH and Days 19-23 for progesterone) in the cycles with orlistat and placebo, respectively, and the one-sided 95% confidence region for the mean in the cycle with orlistat were 1.92, 2.03 and < 2.23 IU 1-1 for LH and 0.147, 0.145 and < 0.176 micrograms 1-1 for progesterone. The one-sided 95% confidence region for the ratio (orlistat/placebo) of geometric means was < 1.06 for LH and < 1.11 for progesterone. CONCLUSION: During normal ovulation the peak serum concentration of LH is above 30 IU 1-1 around Day 14 of the cycle, and that of progesterone exceeds 3 micrograms 1-1 around Day 21. The 95% confidence regions for the means, as well as all individual concentrations, were below these limits. It was concluded that orlistat did not influence the ovulation suppressing action of oral contraceptives.

Adult↗
PubMed1995

A prospective, double-blind, split-subject study on local skin reactions after administration of human menopausal gonadotrophin preparations to healthy female volunteers.

This study was designed to investigate local reactions after the intracutaneous (i.c.) administration of two human menopausal gonadotrophin preparations. For this purpose, 20 healthy female volunteers received six i.c. injections simultaneously, viz. three different batches of both Humegon (Organon, Oss, The Netherlands) and Pergonal (Serono, Geneva, Switzerland) at six different sites on their bodies. Local pain, induration and erythema were registered at 2, 4 and 24 h after administration. No pain was observed. At 4 h after administration, Pergonal-treated sites showed more induration (P = 0.008) and greater surfaces of erythema (P < 0.001) than Humegon-treated sites. Batches of Pergonal showed variation in the surface of erythema induced (P < 0.001), indicating heterogeneity of the batches tested.

Adult↗
PubMed1993

Zatebradine: pharmacokinetics of a novel heart-rate-lowering agent after intravenous infusion and oral administration to healthy subjects.

Zatebradine (1; UL-FS 49 CL; 1,3,4,5-[tetrahydro-7,8-dimethoxy-3-[3-[ [2-(3,4-dimethoxyphenyl)ethyl]methylamino]propyl]-2H-3-benzazepin- 2-on- hydrochloride) is the proposed INN name for a nonchiral, novel, specific heart-rate-lowering drug that is suitable for the treatment of stable angina pectoris. The pharmacokinetics of 1 and of total radioactivity in healthy volunteers (n = 6) were determined after intravenous infusion and oral administration of an experimental drug solution containing 7.5 mg (1.85 MBq) of 14C-labeled drug. Concentrations in plasma and urine were measured by a specific, sensitive, reversed-phase automated high-performance liquid chromatography system with fluorimetric detection at 285 nm Ex, 315 nm Em and by liquid scintillation counting. Recovery of total radioactivity was 89.8 +/- 2.3% (infusion) and 92.2 +/- 3.0% (oral). Renal elimination of total radioactivity was 62.5 +/- 2.0% (infusion) and 48.8 +/- 3.1% (oral). After intravenous infusion and oral administration, 27.3 +/- 2.4 and 43.4 +/- 3.9%, respectively, of the administered dose was eliminated in the feces. Absorption, based on renal excretion of total radioactivity following oral and intravenous dosing, was 79.2 +/- 15.3% (mean +/- standard deviation). Unchanged parent drug contributed 28.4 +/- 5.8% (infusion) and 12.4 +/- 3.7% (oral) of the dose to renal excretion. Zero to three minutes after cessation of the 20-min infusion, the maximum concentration of parent drug in plasma was 161.9 +/- 70.9 ng/mL. After oral administration, a mean peak concentration in plasma of 24.3 +/- 6.7 ng/mL (0.5-3 h postadministration) was reached. Data regarding levels of 1 in plasma could be adequately fitted with an open, two-compartment model.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

No influence of single intravenous doses of omeprazole on theophylline elimination kinetics.

The influence of single intravenous doses of omeprazole on the pharmacokinetics of intravenously administered theophylline was studied in eight healthy male volunteers. In a partially randomized three-period crossover design, an IV infusion of theophylline (400 mg over 30 min) was combined with IV omeprazole (either 40 mg over 2.5 min or 80 mg over 5 min) or with IV placebo (over 2.5 min). Theophylline and omeprazole plasma concentrations were measured over 24 hours after the start of the infusions and pharmacokinetic parameters were calculated. The theophylline plasma concentration-time profiles after omeprazole coadministration were virtually identical to the corresponding profile after placebo administration. For each of the pharmacokinetic parameters of theophylline, the 90% confidence intervals of the omeprazole coadministrations were within the 80 to 120% bioequivalence range with respect to the placebo coadministration. Omeprazole plasma concentrations indicated a biexponential decline in most subjects, with a more rapid elimination after the 40-mg than after the 80-mg dose (P less than .01). Doubling the dose caused an almost three-fold increase of AUC resulting in a difference in clearance (P less than .02), whereas the volume of distribution was similar. The results of this study indicate that the metabolism of theophylline is not affected by single intravenous doses of omeprazole. The nonlinear pharmacokinetics of omeprazole are ascribed to saturation of its main metabolizing enzyme, S-mephenytoin hydroxylase.

Adult↗
PubMed1991

Minor effect of multiple dose omeprazole on the pharmacokinetics of digoxin after a single oral dose.

1. The influence of multiple dose administration of omeprazole on the pharmacokinetics of oral digoxin was studied in 10 healthy male volunteers. 2. In a randomized two-way crossover design a single dose of 1 mg digoxin was administered either alone (control) or on day 8 of an 11 day course of omeprazole 20 mg once daily. 3. Plasma digoxin concentrations were measured over 96 h after digoxin administration with a [125I]-r.i.a. method. 4. On average, Cmax and AUC values for digoxin were approximately 10% higher and tmax tended to be shorter during the administration of omeprazole, while the elimination rate constant was unaffected. 5. The increase in AUC(0,96 h) was statistically significant (P less than 0.05), but within the accepted range for bioequivalence. In two subjects the increase was approximately 30%. 6. It is concluded that co-treatment with omeprazole causes a minor increase in the absorption of oral digoxin. The magnitude of this effect is not considered to be clinically relevant for the majority of patients.

Administration, Oral↗