title: Pharmacokinetics of two generic fixed-dose combinations for HIV-infected children (Pedimune Baby & Pedimune Junior) are similar to the branded products in healthy adults.
abstract: OBJECTIVE
  Cipla Pharmaceuticals have developed generic fixed-dose combinations of stavudine, lamivudine and nevirapine for HIV-infected children (Pedimune Baby and Junior). We determined the pharmacokinetic profiles of stavudine, lamivudine and nevirapine in Pedimune and compared these with the branded products.
  
  
  METHODS
  This Phase I, comparative, single-centre, open-label, three-period, single-dose study was designed as a pilot study to exclude large differences in pharmacokinetics. Six healthy males were randomized to the following regimen sequences: ABC; ACB; BCA; BAC; CAB; CBA (A = reference, B = Pedimune Baby, C = Pedimune Junior). Single doses of medication were administered at 3 time points 4 weeks apart. An 8 h pharmacokinetic curve was recorded at day 1 of every cycle after medication intake. In addition, blood samples were taken on days 2, 3, 4, 8 and 15.
  
  
  RESULTS
  Non-parametric statistical tests revealed no statistically significant differences in Cmax (0.173 < or = P < or = 0.753) and Tmax (0.317 < or = P < or = 1.000) of stavudine, lamivudine and nevirapine between the two Pedimune formulations and the branded drugs. Also, there were no significant differences in AUC(0-infinity) of stavudine, lamivudine and nevirapine between Pedimune Junior and the branded drugs (0.345 < or = P < or = 0.600) and between Pedimune Baby and the branded drug for nevirapine (P = 0.463). In contrast, the AUC(0-infinity) of stavudine (mean change: +21%; P = 0.046) and lamivudine (mean change: +14%; P = 0.028) differed significantly between Pedimune Baby and the branded drugs, but these changes were considered not clinically significant.
  
  
  CONCLUSIONS
  The pharmacokinetic profiles of stavudine, lamivudine and nevirapine in Pedimune Baby and Junior are comparable to the branded products. Based on these results, it is acceptable to test the pharmacokinetics and dosing requirements of Pedimune in HIV-infected children.
authors.affiliation: Department of Clinical Pharmacy, Radboud University Medical Centre, Nijmegen, The Netherlands. R.Lhomme@akf.umcn.nl
authors.forename: Rafaëlla F A
authors.initials: RF
authors.lastname: L'homme
authors.forename: Tim
authors.initials: T
authors.lastname: Dijkema
authors.forename: Adilia
authors.initials: A
authors.lastname: Warris
authors.forename: Andre J A M
authors.initials: AJ
authors.lastname: van der Ven
authors.forename: Diana M
authors.initials: DM
authors.lastname: Gibb
authors.forename: David M
authors.initials: DM
authors.lastname: Burger
mesh_terms: D000328:Adult; D000367:Age Factors; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D016568:Drugs, Generic / Q000493:pharmacokinetics*; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D019259:Lamivudine / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000008:administration & dosage; D010865:Pilot Projects; D018119:Stavudine / Q000008:administration & dosage; D013810:Therapeutic Equivalency
chemical_list: D019380:Anti-HIV Agents; D016568:Drugs, Generic; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine