The effect of ketoconazole on the pharmacokinetics, pharmacodynamics and safety of nisoldipine
| Autor: | R. Heinig, H. G. Adelmann, G Ahr |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Adult
Male Antifungal Agents Time Factors Metabolite Cmax Nisoldipine Pharmacology chemistry.chemical_compound Pharmacokinetics Oral administration medicine Humans Pharmacology (medical) Drug Interactions Cross-Over Studies General Medicine Drug interaction Calcium Channel Blockers Ketoconazole chemistry Pharmacodynamics medicine.drug |
| Zdroj: | European journal of clinical pharmacology. 55(1) |
| ISSN: | 0031-6970 |
| Popis: | Objective: The primary aim of the present study was to investigate the effect of ketoconazole on the pharmacokinetics of nisoldipine. Methods: A single dose of nisoldipine 5 mg immediate-release tablet was administered either alone or in combination with ketoconazole 200 mg (4 days pre-treatment and concomitant administration) in a randomized crossover trial in seven healthy male Caucasian volunteers. Plasma concentration-versus-time profiles of nisoldipine and its metabolite M9 were determined. Results: Pre-treatment with and concomitant administration of ketoconazole resulted in a 24-fold and 11-fold, increase in mean AUC and Cmax of nisoldipine, respectively, compared with treatment with nisoldipine 5 mg alone. The ketoconazole-induced increase in plasma concentration of the metabolite M9 was of similar magnitude. Conclusion: The interaction is attributed to inhibition of cytochrome 3A4-mediated first-pass metabolism. Ketoconazole and other antifungal drugs of the substituted imidazole type as well as other potent inhibitors of cytochrome 3A4 should not be used concomitantly with nisoldipine. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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