Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Dec 2016
Bottom-up Meets Top-down: Complementary Physiologically Based Pharmacokinetic and Population Pharmacokinetic Modeling for Regulatory Approval of a Dosing Algorithm of Valganciclovir in Very Young Children.
Population pharmacokinetic (PopPK) and physiologically based pharmacokinetic (PBPK) models are frequently used to support pediatric drug development. Both methods have strengths and limitations and we used them complementarily to support the regulatory approval of a dosing algorithm for valganciclovir (VGCV) in children <4 months old. ⋯ PBPK and PopPK confirmed that the proposed VGCV dosing algorithm achieves similar GCV exposures in children of all ages and that the alternative dosing algorithm leads to underexposure in a substantial fraction of patients. Our approach raised the confidence in the VGCV dosing algorithm for children <4 months old and supported the regulatory approval.