Pharmacokinetics of nevirapine in HIV-infected children receiving an adult fixed-dose combination of stavudine, lamivudine and nevirapine

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Abstract
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/m2 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 × 106 cells/l and 20.25%, respectively. The median pharmacokinetics parameters were area under the curve at 12 h, 78.4 h × μg/ml; minimum plasma drug concentration, 5.98 μg/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 μg/ml (2.57 μg/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 × 106 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.

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