Single oral dose pharmacokinetic interaction study of manidipine and delapril in healthy volunteers
| Autor: | Simone Lens, Daniela Acerbi, Armel Stockis, Gianluigi Poli, Christophe Gengler, Fabienne Goethals, Bernard Jeanbaptiste |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Adult
Male Dihydropyridines Metabolite Delapril Biological Availability Angiotensin-Converting Enzyme Inhibitors Pharmacology Mass Spectrometry Piperazines chemistry.chemical_compound Manidipine Pharmacokinetics Oral administration Drug Discovery medicine Humans Drug Interactions Active metabolite Nitrobenzenes Cross-Over Studies Calcium Channel Blockers Crossover study Bioavailability Drug Combinations chemistry Area Under Curve Indans medicine.drug Chromatography Liquid Half-Life |
| Zdroj: | Arzneimittel-Forschung. 53(9) |
| ISSN: | 0004-4172 |
| Popis: | 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 andlor of delapril and metabolites M1, M2 and M3, using specific LC-MSIMS methods. Results: The bioavailability of manidipine and M-XIII was slightly decreased by concomitant administration of delapril (manidipine: C max -19 % and AUC -11 %; M-XIII: C max -17 % and AUC t -18 %). The bioavailability of delapril was not influenced by co-administration with manidipine (C max -7 % and AUC +4 %). The effect on delapril pharmacologically active metabolites MI and M3 was negligible. The inactive metabolite M2 underwent a 13 % reduction of C max and AUC . The 90 % confidence intervals were confined within limits of acceptance (70-143% for C max 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. |
| Databáze: | OpenAIRE |
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