ISSN:
1432-1041
Schlagwort(e):
Key words Enzyme inhibition
;
Cytochrome P450 3A4
;
First-pass metabolism
;
Bioavailability
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Chemie und Pharmazie
,
Medizin
Notizen:
Abstract 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.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/s002280050593
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