title: Single-dose pharmacokinetic properties, bioavailability, and tolerability of two lamivudine 100-mg tablet formulations: a randomized crossover study in healthy Chinese male subjects.
abstract: BACKGROUND
  Lamivudine is used in the treatment of HIV and chronic hepatitis B (HBV) infections. Since 1999, at least 2 million Chinese HBV patients have been treated with lamivudine, but there are limited studies on the pharmacokinetics and safety of the drug in Chinese populations.
  
  
  OBJECTIVE
  This study was designed to assess the bioequivalence of a newly developed lamivudine tablet (test drug) and a branded lamivudine tablet (reference drug) in healthy Chinese male volunteers.
  
  
  METHODS
  A single-center, single-dose, randomized, open-label, 2-period crossover study was conducted in 28 healthy Chinese male volunteers. Blood samples were collected up to 24 hours after the administration of oral lamivudine 100 mg in each period. Plasma lamivudine concentrations were analyzed by a validated LC-MS/MS method. Pharmacokinetic and bioavailability parameters were calculated. Adverse events (AEs) were recorded.
  
  
  RESULTS
  There were no significant differences in mean (SD) pharmacokinetic parameters between the test and reference drugs, including Cmax (1239 [328.9] ng/mL vs 1176 [341.5] ng/mL), AUC0-t (4096 [599.1] ng · h/mL vs 4064 [678.2] ng · h/mL), and AUC0-∞ (4200 [607.7] ng · h/mL vs 4162 [672.2] ng · h/mL). The geometric mean test/reference ratios (90% CI) calculated for the log-transformed parameters were Cmax, 1.06 (96.21-116.90); AUC0-t, 1.01 (96.53-105.39); and AUC0-∞, 1.01 (96.81-105.16), all of which were within the acceptance limits for bioequivalence. No serious AEs were reported, and all mild AEs were recovered quickly without treatment.
  
  
  CONCLUSIONS
  These findings suggest that the test formulation of lamivudine 100 mg meets the FDA regulatory standards for bioequivalence with the reference formulation. Both formulations were well tolerated.
authors.affiliation: Phase I Clinical Trial Unit, China-Frontage USA, The First Hospital of Jilin University, Changchun, People's Republic of China.
authors.forename: Xiaojiao
authors.initials: X
authors.lastname: Li
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Yanfu
authors.initials: Y
authors.lastname: Sun
authors.forename: Haiyan
authors.initials: H
authors.lastname: Chen
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Ding
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D044466:Asian People; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D064368:Healthy Volunteers; D019694:Hepatitis B, Chronic / Q000188:drug therapy; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013607:Tablets; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D018894:Reverse Transcriptase Inhibitors; D013607:Tablets; D019259:Lamivudine
keywords: Chinese male volunteers; LC–MS/MS; bioequivalence; lamivudine; pharmacokinetics