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

摘要

AIMS: To develop a population pharmacokinetic model for stavudine in children and to investigate the consistency of the currently recommended dose based on adult target concentrations. METHODS: The pharmacokinetics of stavudine were investigated using a population approach. Individual estimates of CL/F were used to calculate the stavudine dose required to achieve the area under the concentration-time curve reported in adults given recommended doses. RESULTS: Stavudine pharmacokinetics were well described by a one-compartment model with zero-order absorption. Typical population estimates (% interindividual variability) of the apparent distribution volume (V/F) and plasma clearance (CL/F) were 40.9 l (32%) and 16.5 l h(-1) (38%), respectively. Stavudine V/F and CL/F were similarly related to age. Mean calculated doses (0.61 mg kg(-1) for children less than 2 weeks, 1.23 mg kg(-1) for children more than 2 weeks with bodyweight less than 30 kg, and 31.5 mg for children with a bodyweight between 30 and 60 kg) were in agreement with the current paediatric doses (0.5 mg kg(-1), 1 mg kg(-1), and 30 mg, respectively). CONCLUSIONS: Our findings support the current recommended paediatric dosage regimens for stavudine, as they result in the same exposure to the drug as in adults.