title: Steady-state pharmacokinetic comparison of generic and branded formulations of stavudine, lamivudine and nevirapine in HIV-infected Ugandan adults.
abstract: BACKGROUND
  We aimed to compare the steady-state pharmacokinetic parameters and tolerability of Triomune 40 (stavudine 40 mg, lamivudine 150 mg and nevirapine 200 mg) and branded formulations of these drugs in HIV-infected Ugandans.
  
  
  METHODS
  This includes a randomized, open-label, cross-over study of HIV-infected patients stable on therapy for 1 month. Patients were randomized to generic or branded formulation. Plasma pharmacokinetics were assessed after 1 month. The following day, alternate formulation was administered, and 1 month later, drug pharmacokinetics were re-assessed. Plasma pharmacokinetics were determined using HPLC-UV detection. Similarity between steady-state pharmacokinetic parameters was assessed using the US Food and Drug Administration standards for bioequivalency testing. Tolerability was assessed using questionnaires.
  
  
  RESULTS
  Sixteen (10 females) patients completed the study. Median (IQR) age, weight and CD4 count were 37 (33.7-40) years, 65 (63.4-66) kg and 292 (220.7-344.5) cells/mm(3), respectively. All patients received co-trimoxazole. The geometric mean ratio (90% CI) for stavudine, lamivudine and nevirapine was 0.92 (0.78-1.08), 1.11 (0.95-1.30) and 0.84 (0.64-1.11), respectively, for C(max), and 0.83 (0.70-0.97), 1.06 (0.94-1.20) and 0.88 (0.71-1.10), respectively, for AUC. Stavudine plasma concentrations were significantly lower for the generic formulation. Pharmacokinetic parameter inter-individual variability ranged from 29% to 99%. There were no differences in tolerability for the two formulations.
  
  
  CONCLUSIONS
  Pharmacokinetic profiles of generic and branded drugs were similar. Differences particularly with regard to stavudine were demonstrated. Surveillance of the quality of generic antiretroviral drugs in the target populations is needed. Capacity building for pharmacokinetic research in resource-limited settings is a priority.
authors.affiliation: Research Department, Makerere University Infectious Diseases Institute, Kampala, Uganda. pbyakika@idi.co.ug
authors.forename: Pauline
authors.initials: P
authors.lastname: Byakika-Kibwika
authors.forename: Mohammed
authors.initials: M
authors.lastname: Lamorde
authors.forename: Francis
authors.initials: F
authors.lastname: Kalemeera
authors.forename: Antonio
authors.initials: A
authors.lastname: D'Avolio
authors.forename: Sciandra
authors.initials: S
authors.lastname: Mauro
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Perri
authors.forename: Mairin
authors.initials: M
authors.lastname: Ryan
authors.forename: Harriet
authors.initials: H
authors.lastname: Mayanja-Kizza
authors.forename: Saye
authors.initials: S
authors.lastname: Khoo
authors.forename: David
authors.initials: D
authors.lastname: Back
authors.forename: Marta
authors.initials: M
authors.lastname: Boffito
authors.forename: Concepta
authors.initials: C
authors.lastname: Merry
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D016568:Drugs, Generic / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010949:Plasma / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D018119:Stavudine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011795:Surveys and Questionnaires; D014454:Uganda
chemical_list: D019380:Anti-HIV Agents; D016568:Drugs, Generic; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine