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Eur J Clin Pharmacol. 1999 Mar;55(1):57-60.

The effect of ketoconazole on the pharmacokinetics, pharmacodynamics and safety of nisoldipine.

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1
Institute of Clinical Pharmacology, Bayer AG, Wuppertal, Germany.

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 pretreatment 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.

PMID:
10206086
DOI:
10.1007/s002280050593
[Indexed for MEDLINE]

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