Age‐related differences in the pharmacokinetics of stavudine in 272 children from birth to 16 years: a population analysis

Abstract

-1 , 1 mg kg -1 , and 30 mg, respectively). ConclusionsOur findings support the current recommended paediatric dosage regimens for stavudine, as they result in the same exposure to the drug as in adults.

Estimation of Intracellular Concentration of Stavudine Triphosphate in HIV-Infected Children Given a Reduced Dose of 0.5 Milligrams per Kilogram Twice Daily

“…1, right panel), as reported by Jullien et al (12). Our 95% PI of stavudine plasma concentration in children encompassed the upper half of the data reported by Jullien et al (12).…”

“…The predictability of the model in pediatric patients was evaluated based on the simulation of a dose of 1.23 mg/kg superimposed over the stavudine plasma concentrations from 272 children who were administered the same dose (Fig. 1, right panel), as reported by Jullien et al (12). Our 95% PI of stavudine plasma concentration in children encompassed the upper half of the data reported by Jullien et al (12).…”

“…As age is an independent predictor of volume of distribution for stavudine in prepubertal children (12), it was incorporated as a covariate of V in the pediatric simulation. Weights of children ranging from 6 to 30 kg and at ages from 0.5 to 9 years were then used to evaluate whether the predicted stavudine exposure using our model in this weight range was consistent with the pediatric data from Jullien et al (12). The predictability of the model in pediatric patients was evaluated based on the simulation of a dose of 1.23 mg/kg superimposed over the stavudine plasma concentrations from 272 children who were administered the same dose (Fig.…”

“…The population pharmacokinetic model for stavudine in pediatric patients, previously developed by Jullien et al (12), was based on a one-compartment model with first-order elimination and zero-order absorption. Age, rather than weight, was a significant covariate of both CL/F and V/F in newborns through 16 years of age.…”

“…The current standard pediatric dose of stavudine, 1 mg/kg twice daily (BID), was established by extrapolation from the plasma pharmacokinetic (PK) parameters of the adult dose by using data from a few small, wellcontrolled pediatric pharmacokinetic studies. Those studies showed that an oral dose of 1 mg/kg BID in children under 30 kg gives plasma exposure similar to that of 40 mg BID in adults weighing more than 60 kg and that an oral dose of 0.5 mg/kg BID in children gives plasma exposure similar to that of adults taking 20 mg BID (10)(11)(12). Preapproval adult dose-finding studies performed in the 1990s found that 20 mg BID and 40 mg BID had equivalent antiviral effects (13)(14)(15)(16).…”