Pharmacokinetics of nevirapine in HIV-infected children receiving an adult fixed-dose combination of stavudine, lamivudine and nevirapine.
OBJECTIVE
To evaluate the steady state pharmacokinetics of nevirapine (NVP) in HIV-infected children receiving a fixed-dose combination of stavudine, lamivudine and NVP.


METHODS
This cross-sectional study enrolled 34 children (18 girls) who had received GPO-VIR S30 (30 mg stavudine, 150 mg lamivudine and 200 mg NVP) for at least 8 weeks. Tablets were divided into quarter fractions (1/4, 1/2, 3/4 or 1 tablet) to attain the NVP dosages of 120-200 mg/m every 12 h. Plasma NVP levels were measured at predose, and at 2 and 6 h after drug administration.


RESULTS
The median age was 8.4 years (range, 3-15). Median CD4 lymphocyte count and percentage at study entry was 576 x 10 cells/l and 20.25%, respectively. The median pharmacokinetics parameters were area under the curve at 12 h, 78.4 h x mug/ml; minimum plasma drug concentration, 5.98 microg/ml; plasma half-life, 25.5 h; apparent oral clearance, 0.079 l/kg per h; and volume of distribution, 2.95 l/kg. Only one child had a minimum plasma drug concentration < 3.4 microg/ml (2.57 microg/ml). Of the 13 children who received GPO-VIR as their first-line regimen, 12 had plasma HIV-1 RNA < 400 copies/ml at 6-18 months, with a median CD4 lymphocyte increase of 216 and 433 x 10 cells/l at 6 and 12 months of treatment, respectively.


CONCLUSIONS
The administration of GPO-VIR S30 fixed-dose combination tablets in fractions or as a whole tablet to children resulted in appropriate NVP exposure and satisfactory virological and immunological benefit. This finding confirms the effectiveness of using a fixed-dose combination as a "transitional option" while waiting for a paediatric fixed-dose combination drug formulation.
Chokephaibulkit
Kulkanya
K
Department of Pediatrics, Faculty of Medicine-Siriraj Hospital, 2 Prannok Road, Bangkok-noi, Bangkok 10700, Thailand. sikch@mahidol.ac.th
Plipat
Nottasorn
N
Cressey
Tim R
TR
Frederix
Koen
K
Phongsamart
Wanatpreeya
W
Capparelli
Edmund
E
Kolladarungkri
Teera
T
Vanprapar
Nirun
N
D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D023241:Antiretroviral Therapy, Highly Active; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004338:Drug Combinations; D004341:Drug Evaluation; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D019259:Lamivudine / Q000008:administration & dosage*; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018119:Stavudine / Q000008:administration & dosage*; D013607:Tablets
D019380:Anti-HIV Agents; D004338:Drug Combinations; D013607:Tablets; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine