title: Pharmacokinetic comparison of generic and trade formulations of lamivudine, stavudine and nevirapine in HIV-infected Malawian adults.
abstract: BACKGROUND
  The Malawian antiretroviral program uses generic Triomune (stavudine, lamivudine, and nevirapine).
  
  
  OBJECTIVE
  To determine the pharmacokinetics and bioequivalence of generic and trade formulations of stavudine, lamivudine, and nevirapine in HIV-infected Malawians.
  
  
  METHODS
  This randomized, open label, cross-over study comprised of six men and six women currently receiving Triomune-40 TM who were randomized to the generic or trade formulation of stavudine (40 mg twice daily), lamivudine (150 mg twice daily) and nevirapine (200 mg twice daily). After at least 21 days, the alternate formulation was administered. At the end of each period, six blood samples were collected over 8 h. Bioequivalence was achieved if the 90% confidence interval (CI) for the geometric mean ratio (GMR) of generic:trade formulations for maximum plasma concentration (Cmax) and the area under the concentration-time curve (AUC) was within 0.8-1.25.
  
  
  RESULTS
  Mean patient age, weight, and height were 38.4 years (SD, 7.7), 71.2 kg (SD, 7.0), and 164.8 cm (SD, 6.3), respectively. The GMR for stavudine, lamivudine, and nevirapine were 1.4 (90% CI, 1.2-1.7), 1.1 (90% CI, 0.8-1.6), and 0.9 (90% CI, 0.7-1.2), respectively, for Cmax; and 1.1 (90% CI, 1.0 1.2), 1.0 (90% CI, 0.7-1.3), and 0.9 (90% CI, 0.7-1.1), respectively, for AUC0-8h. Regardless of formulation, Malawians had higher nevirapine exposures compared with historical reports of Western HIV-infected patients.
  
  
  CONCLUSIONS
  Although exposures were similar, Triomune did not meet the strict definition of bioequivalence for these drugs. Patients taking Triomune had notably higher stavudine Cmax values. Antiretroviral pharmacokinetics and bioequivalence of generic formulations should be evaluated in the populations in which they are being used.
authors.affiliation: University of North Carolina Project, Lilongwe Malawi.
authors.forename: Mina C
authors.initials: MC
authors.lastname: Hosseinipour
authors.forename: Amanda H
authors.initials: AH
authors.lastname: Corbett
authors.forename: Cecelia
authors.initials: C
authors.lastname: Kanyama
authors.forename: Idah
authors.initials: I
authors.lastname: Mshali
authors.forename: Severiano
authors.initials: S
authors.lastname: Phakati
authors.forename: Nazer L
authors.initials: NL
authors.lastname: Rezk
authors.forename: Charles
authors.initials: C
authors.lastname: van der Horst
authors.forename: Angela D M
authors.initials: AD
authors.lastname: Kashuba
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D023241:Antiretroviral Therapy, Highly Active; D019540:Area Under Curve; D018791:CD4 Lymphocyte Count; D016001:Confidence Intervals; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D016568:Drugs, Generic / Q000493:pharmacokinetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D019259:Lamivudine / Q000493:pharmacokinetics*; D008295:Malawi; D008297:Male; D019829:Nevirapine / Q000493:pharmacokinetics*; D018119:Stavudine / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D016568:Drugs, Generic; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine