Pharmacokinetics of two generic fixed-dose combinations for HIV-infected children (Pedimune Baby & Pedimune Junior) are similar to the branded products in healthy adults.
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.
L'homme
Rafaëlla F A
RF
Department of Clinical Pharmacy, Radboud University Medical Centre, Nijmegen, The Netherlands. R.Lhomme@akf.umcn.nl
Dijkema
Tim
T
Warris
Adilia
A
van der Ven
Andre J A M
AJ
Gibb
Diana M
DM
Burger
David M
DM
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
D019380:Anti-HIV Agents; D016568:Drugs, Generic; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine