Determination of lamivudine in human plasma by HPLC and its use in bioequivalence studies.
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.
Kano
Eunice Kazue
EK
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.
dos Reis Serra
Cristina Helena
CH
Koono
Eunice Emiko Mori
EE
Andrade
Simone Schramm
SS
Porta
Valentina
V
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
D019380:Anti-HIV Agents; D019259:Lamivudine; D018119:Stavudine