The aim of this study was to simulate pediatric pharmacokinetic parameters using data from a clinical trial in healthy adults who were administered a pediatric fixed-dose combination of lamivudine (3TC)/zidovudine (AZT)/ nevirapine (NVP) (30/60/50 mg) granules for reconstitution and fast disintegrating tablets. Using the area under the curve (AUC) from noncompartmental analysis, the relative bioavailability of the test suspension and test tablet to the reference suspension was 93.7% and 104.5% for lamivudine, 82.9% and 97.9% for nevirapine, and 94.2% and 93.6% for zidovudine, respectively. The 90% CI for Cmax, AUC0–t, and AUCt–∞ were 85.69%–102.54%, 96.13%–117.79%, and 82.63%–106.72%, respectively, for lamivudine; 83.33%–109.15%, 99.94%–124.54%, and 98.22%–122.43%, respectively, for zidovudine; and 87.71%–109.20%, 89.31%–106.26%, and 85.95%–102.82%, respectively, for nevirapine. Pharmacokinetic parameters were generated using the pharmacokinetics (PK) PKTM module in GastroPlus® modeling and simulation software. Pediatric pharmacokinetic parameters were simulated using adult clinical data and pediatric physiologic variables as inputs to the PKTM module. The resulting virtual pediatric subjects’ PK data were regressed against pediatric body weight (BW), body surface area (BSA), and postgestational age (PGA), respectively. Clearance and volume of distribution were linearly correlated with BW (R2 = 1.000) but obeyed the polynomial equation of the third order with the PGA of the subjects (R2 ubjects . Simulation of pediatric pharmacokinetic parameters using adult PK data and pediatric physiologic parameters as input produced pediatric PK total clearance and volume of distribution, which were linearly correlated with BW but polynomially correlated with the PGA of children. By making appropriate allowances for a specific enzyme’s maturation rate and presence, allometric scaling of pediatric doses of antiretroviral drugs lamivudine, nevirapine, and zidovudine could be more reliably determined using a linear expression based on BW and BSA and polynomial expression based on child’s PGA of up 12 years.
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