A. Stockis, Christophe Gengler, F. Goethals
Sep 1, 2003
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0
Influential Citations
10
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Journal
Arzneimittelforschung
Abstract
Summary Objective: The objective of the study was to assess potential pharmacokinetic interactions between delapril, an angiotensin conversion enzyme inhibitor, and manidipine, a calcium channel antagonist, prior to the development of a fixed combination drug product. Methods: Eighteen healthy male volunteers received a single oral dose of 10 mg manidipine dihydrochloride (CAS 89226-75-5), or 30 mg delapril hydrochloride (CAS 83435-67-0), or both simultaneously, according to a fully balanced three-way cross-over design. The three treatments were separated by a one-week washout period. Blood samples were collected during 24 h for plasma determination of manidipine and metabolite M-XIII and/or of delapril and metabolites M1, M2 and M3, using specific LC-MS/MS methods. Results: The bioavailability of manidipine and M-XIII was slgihtly decreased by concomitant administration of delapril (manidipine: Cmax − 19 % and AUC∞ − 11 %; M-XIII: Cmax − 17 % and AUCt − 18 %). The bioavailability of delapril was not influenced by co-administration with manidipine (Cmax − 7 % and AUC∞ +4 %). The effect on delapril pharmacologically active metabolites M1 and M3 was negligible. The inactive metabolite M2 under-went a 13 % reduction of Cmax and AUC∞ . The 90 % confidence intervals were confined within limits of acceptance (70 − 143 % for Cmax and 80 − 125 % for AUC). Mean residence times and apparent elimination half-lives were unaltered. Blood pressure and heart rate versus time profiles were similar during the three treatments. Conclusion: Simultaneous oral administration of 10 mg manidipine and 30 mg delapril does not significantly alter the pharmacokinetics of either drug or that of their principal metabolites.