Background Raltegravir is a drug used to treat patients with HIV infection. Understanding the disposition kinetics including the ontogeny of the major metabolic enzyme (UGT1A1) is important in prediction of raltaeravir pharmacokinetics in paediatric patients.

Methods Sim-Raltegravir compound file in Simcyp simulator version 18 was used to predict pharmacokinetics in paediatric subjects aged 4 weeks to 6 months, 0.5 to 2, 2 to 6 and 6 to 12 years. Details of trial design were matched as closely as possible with a clinical study.¹ Rate of absorption and variability in first order absorption model within Simcyp were set to the reported values. Predicted plasma concentration time profiles with 5th and 95th percentile were compared with observations.

Results The predicted vs. observed geometric mean area under plasma concentration-time profile of raltegravir was 18.4 vs. 22.3 µM.h in subjects 4 weeks to 6 months and 16.5 vs. 19.8 µM.h in those 0.5 to 2 years old. In 2 to 6 and 6 to 12 year olds around 80% and 85% of observed data were within 5th and 95th percentile of the predictions.

Conclusion The results show that the UGT1A1 ontogeny profile in the Simcyp version 18 adequately addressed age-related differences in pharmacokinetics of raltegravir.

Reference

1. Rizk, M., et al, J Clin Pharmacol 2015; 55(7):748–56

Disclosure(s) Nothing to disclose