Thalidomide does not alter estrogen-progesterone hormone single dose pharmacokinetics
| Autor: | Karin A. Kook, Wayne Colburn, Michael R. Scheffler, Steve D. Thomas |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Adult
medicine.medical_specialty Norethisterone Antineoplastic Agents Hormonal medicine.drug_class Administration Oral Leprostatic Agents Pharmacology Ethinyl Estradiol Drug Administration Schedule Pharmacokinetics Elimination rate constant Oral administration Reference Values Internal medicine Ethinylestradiol medicine Humans Hypnotics and Sedatives Pharmacology (medical) Cross-Over Studies Chemistry Crossover study Contraceptives Oral Synthetic Thalidomide Endocrinology Estrogen Area Under Curve Female Dermatologic Agents Norethindrone hormones hormone substitutes and hormone antagonists medicine.drug Half-Life |
| Zdroj: | Clinical pharmacology and therapeutics. 65(5) |
| ISSN: | 0009-9236 |
| Popis: | Objectives To determine the single- and multiple-dose pharmacokinetics of oral thalidomide (200 mg/day, administered for 21 days) and to assess the effects of steady-state plasma concentrations of thalidomide on the single-dose pharmacokinetics of ethinyl estradiol (INN, ethinylestradiol) and norethindrone (INN, norethisterone). Methods A randomized, 2-period crossover study was performed in 10 healthy premenopausal female volunteers. The pharmacokinetic profiles of plasma concentrations of thalidomide were evaluated with both noncompartmental and compartmental methods, whereas those of ethinyl estradiol and norethindrone were calculated with noncompartmental methods. The effects of steady-state plasma thalidomide concentrations on the pharmacokinetics of ethinyl estradiol and norethindrone were determined with use of an ANOVA model that included treatment sequence, subject within sequence, period, and treatment as factors. Results Thalidomide plasma concentrations were best predicted by a 1-compartment model with first-order absorption and elimination and an absorption time-lag. There were no significant differences between pharmacokinetic parameters for thalidomide after 1 dose and those after 18 consecutive doses. Except for a minor decrease of the elimination rate constant (ke) for ethinyl estradiol, coadministration of thalidomide had no significant effects on the pharmacokinetic profiles for either ethinyl estradiol or norethindrone. The change in ke for ethinyl estradiol during thalidomide administration was not associated with any alteration in the clearance or elimination half-life for this hormone. Conclusions Multiple-dose pharmacokinetics of thalidomide is similar to the single-dose profile. This study did not investigate the efficacy of the 21-day fixed ethinyl estradiol–norethindrone regimen, but the results suggest that thalidomide is unlikely to affect the pharmacokinetics of orally administered hormonal contraceptives. Clinical Pharmacology & Therapeutics (1999) 65, 483–490; doi |
| Databáze: | OpenAIRE |
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