Prediction of Voriconazole Non-linear Pharmacokinetics Using a Pediatric Physiologically-based Pharmacokinetic Modeling Approach

We read with interest the report by Zane and Thakker entitled ‘‘A PBPK model for voriconazole disposition predicts intestinal first-pass metabolism in children’’.

We believe the authors should be congratulated for tackling the complex case of voriconazole, as this is a drug with non-linear pharmacokinetics where clinical trials have shown a marked difference between adults and children. Hence, we find the report timely and the attempt to develop a physiologically based pharmacokinetic (PBPK) model worthwhile, not just for this case but as a general demonstration for the approaches that can be taken. The authors also highlight the fact that intestinal first-pass metabolism might be an important factor contributing to the lower bioavailability observed in children compared with adults.

Author(s): Trevor Johnson, Farzaneh Salem, Masoud Jamei, Amin Rostami-Hodjegan

Year: May 1, 2015