Population pharmacokinetics of abacavir in infants, toddlers and children

摘要: Aims To characterize the pharmacokinetics of abacavir in infants, toddlers and children to assess influence covariates on drug disposition across these populations. Methods Abacavir concentration data from three clinical studies human immunodeficiency virus-infected (n = 69) were used for model building. The received either a weight-normalized dose 16 mg kg−1 day−1 or World Health Organization recommended based weight bands. A population pharmacokinetic analysis was performed using nonlinear mixed effects modelling VI. age, gender, bodyweight formulation evaluated. final selected according graphical statistical criteria. Results A two-compartmental with first-order absorption elimination best described abacavir. Bodyweight identified as significant covariate influencing apparent oral clearance volume distribution. Predicted steady-state maximal plasma area under concentration–time curve 0 12 h standard twice daily regimen 2.5 mg l−1 6.1 mg h l−1 3.6 mg l−1 8.7 mg h l−1 children, respectively. Model-based predictions showed that equivalent systemic exposure achieved after once dosing regimens. There no differences between two formulations (tablet solution). demonstrated good predictive performance prediction individual patients and, such, can be support therapeutic monitoring conjunction sparse sampling. Conclusions The appears affected only by size, irrespective patient's age. Maturation processes metabolism younger infants should evaluated further demonstrate potential impact ontogeny.