HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Sign In to gain access to subscriptions and/or personal tools.

This Article Full Text Full Text (PDF) All Versions of this Article: 0091270008327536v1 49/2/205    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Request Reprints Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Boralli, V. B. Articles by Lanchote, V. L. Search for Related Content PubMed PubMed Citation Articles by Boralli, V. B. Articles by Lanchote, V. L. Social Bookmarking                         What's this?

Enantioselectivity in the Pharmacokinetic Interaction Between Fluvastatin and Lercanidipine in Healthy Volunteers

From the Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brasil (Dr Boralli, Dr Sampaio, Dr Marques, Dr Lanchote) and Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brasil (Dr Coelho).

Hypertension and dyslipidemia are independent risk factors for cardiovascular mortality and are frequently present in the same patient. Fluvastatin (FV), used to reduce cholesterol levels, and lercanidipine (LER), used to control blood pressure, are marketed as racemic mixtures. Therapeutic activities are 30-fold higher for (+)-3R, 5S-FV and 100- to 200-fold higher for S-LER compared with their respective antipodes. The present study describes the enantioselective pharmacokinetic interaction between LER and FV in healthy volunteers. A crossover randomized study was conducted in 3 phases on 8 volunteers treated with a single oral racemic dose of LER (20 mg) or FV (40 mg) or LER plus FV. Serial blood samples were collected from 0 to 24 hours. Plasma concentrations of the LER and FV enantiomers were determined by liquid chromatography/tandem mass spectrometry, and pharmacokinetic parameters were evaluated using the WinNonlin software. The Wilcoxon and Mann-Whitney tests (P < .05) were used to analyze enantiomer ratios and the pharmacokinetic drug interaction. Data are expressed as medians. In monotherapy, the kinetic disposition of both FV and LER was enantioselective. AUC values were significantly higher for (-)-3S,5R-FV than for (+)-3R,5S-FV (358.20 vs 279.68 ng·h/mL) and for S-LER compared with R-LER (13.90 vs 11.88 ng·h/mL). The pharmacokinetic parameters of FV were not enantioselective when combined with LER (AUC: (-)-3S,5R-FV: 325.21; (+)-3R,5S-FV: 316.44 ng·h/mL). There was a significant reduction in S-LER (8.06 vs 13.90 ng·h/mL) and R-LER (6.76 vs 11.88 ng·h/mL) AUC values when FV was coadministered. In conclusion, the interaction between FV-LER might be clinically relevant because AUC values of (+)-3R,5S-FV were increased when LER was coadministered, and AUC values of the 2 LER enantiomers were reduced when FV was coadministered.

Key Words: Lercanidipine • fluvastatin • drug-drug interaction • enantiomers • pharmacokinetics • healthy volunteers

Address for reprints: Vera Lucia Lanchote, PhD, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-USP, Departamento de Análises Clínicas, Toxicológicas and Bromatológicas, Avenida do Café s.n. Campus da USP, 14040-903, Ribeirão Preto, SP, Brazil; e-mail: lanchote{at}fcfrp.usp.br.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?