title: Determination of lamivudine in human plasma by HPLC and its use in bioequivalence studies.
abstract: A simple, accurate, precise and sensitive high-performance liquid chromatographic (HPLC) method with ultraviolet detection was developed to quantificate lamivudine (3-TC) in human plasma samples from bioequivalence studies. 3-TC and stavudine (internal standard, I.S.) were extracted from 0.5 ml of human plasma by acetonitrile protein precipitation. The method was validated over a concentration range of 0.05-3.00 microg/ml and used in a bioequivalence trial between two lamivudine formulations, to assess its usefulness in this kind of study. FURP-lamivudine (Fundação para o Remédio Popular, Brazil, as test formulation) and Epivir (GlaxoSmithKline, Brazil, as reference formulation) were evaluated following a single 150 mg oral dose to 24 healthy volunteers of both genders. The dose was administered after an overnight fast according to a two-way crossover design. Bioequivalence between the products was determined by calculating 90% confidence intervals (90% CI) for the ratio of Cmax, AUC0-t and AUC0-inf values for the test and reference products, using logarithmic transformed data. The 90% confidence intervals for the ratio of Cmax (0.86-1.06), AUC0-t (0.96-1.04) and AUC0-inf (0.97-1.05) values for the test and reference products are within the 0.80-1.25 interval proposed by FDA and EMEA. It was concluded that the two 3-TC formulations are bioequivalent in their rate and extent of absorption, and thus, may be used interchangeably.
authors.affiliation: Departamento de Farmácia, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Av. Professor Lineu Prestes 580, Bloco 15, Cidade Universitária Armando Salles Oliveira, CEP 05508-900 São Paulo, Brazil.
authors.forename: Eunice Kazue
authors.initials: EK
authors.lastname: Kano
authors.forename: Cristina Helena
authors.initials: CH
authors.lastname: dos Reis Serra
authors.forename: Eunice Emiko Mori
authors.initials: EE
authors.lastname: Koono
authors.forename: Simone Schramm
authors.initials: SS
authors.lastname: Andrade
authors.forename: Valentina
authors.initials: V
authors.lastname: Porta
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000097:blood* / Q000493:pharmacokinetics; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D019259:Lamivudine / Q000097:blood* / Q000493:pharmacokinetics; D008297:Male; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet; D018119:Stavudine / Q000097:blood; D013810:Therapeutic Equivalency
chemical_list: D019380:Anti-HIV Agents; D019259:Lamivudine; D018119:Stavudine