title: Bioequivalence evaluation of 2 tablet formulations of entecavir in healthy chinese volunteers: a single-dose, randomized-sequence, open-label crossover study.
abstract: A randomized, 2-way crossover study was conducted in healthy Chinese male volunteers to evaluate the bioequivalence of a new generic formulation of entecavir (CAS 142217-69-4) tablets (test) and the available branded formulation (reference) to meet the requirements for marketing the test product in China. Test and reference tablets were administered as a single dose on 2 treatment days separated by a 2-week washout period. Blood samples were collected for a period of 24 h following drug administration. Plasma concentration of entecavir was determined by a liquid chromatography-tandem mass spectrometry (LC/MS/MS) method. Pharmacokinetic parameters were calculated using a noncompartmental model. Bioequivalence was determined by calculating 90% CIs for the ratios of Cmax, AUC0-t and AUC0-∞ values for the test and reference products. Tolerability was assessed by monitoring vital signs, laboratory tests and interviews with the volunteers before administration and every 2 h during the study. The 90% CIs of entecavir for Cmax, AUC0-t and AUC0-∞ were 95.2-106.9%, 98.4-104.6% and 97.3-104.4%, respectively, which fell within the interval of 80-125%. No clinically important adverse effects were reported. These results suggested that the test formulation of entecavir tablets met the regulatory criterion for bioequivalence to the reference formulation.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Jin
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: L
authors.initials: L
authors.lastname: Zhao
authors.forename: Z
authors.initials: Z
authors.lastname: Ma
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: M
authors.initials: M
authors.lastname: Huang
authors.forename: G
authors.initials: G
authors.lastname: Zhong
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D008297:Male; D053719:Tandem Mass Spectrometry; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; C413685:entecavir; D006147:Guanine