938

Introduction: The purpose of paediatric pharmacokinetic studies is to provide precise estimates of the true value of pharmacokinetic parameters to inform dosing. Hypothesis: We evaluated age-groups studied and the precision of parameter estimates in peer-reviewed pharmacokinetic studies. Methods: Systematic reviews of 10 drugs included publications describing >1 pharmacokinetic study in patients <18 years. A pharmacokinetic study was defined as peer-reviewed primary data used to estimate one or more of the pharmacokinetic parameters: volume of distribution (Vd), clearance (CL), or half-life (HL). We defined uncertainty as the width of the 95% confidence interval divided by the study mean, and acceptable uncertainty as uncertainty <20%. We sought age-specific data for each of 5 pre-defined age groups for each drug. Results: Review of 6207 abstracts identified 114 eligible manuscripts containing 171 pharmacokinetic studies and 425 pharmacokinetic parameter estimates (145 Vd, 150 CL, 130 HL) and 364 uncertainty intervals. The median(IQR) sample size was 14(8-30). Estimates were derived from single age groups in 72(42.11%) studies however 28(56%) of the 50 drug/age-group pairs had no group-specific data. Acceptable uncertainty was found in 21(16.67%) Vd, 29(25.22%) HL, and 37(30.08%) CL estimates. Groups of potentially similar single-age studies were heterogeneous. Conclusions: Review of 10 commonly administered drugs found missing age-specific data was common. Available data were imprecise and not amenable to meta-analytic synthesis. Potential sources of variability included small sample sizes. Peer-reviewed pharmacokinetic data for children is incomplete, when available is imprecise, is likely to be a major source of dosing error and threat to the provision of optimal pharmacotherapy to children.