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.
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Received: 8 September 1998 / Accepted in revised form: 23 November 1998
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Heinig, R., Adelmann, H. & Ahr, G. The effect of ketoconazole on the pharmacokinetics, pharmacodynamics and safety of nisoldipine. E J Clin Pharmacol 55, 57–60 (1999). https://doi.org/10.1007/s002280050593
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DOI: https://doi.org/10.1007/s002280050593