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Prediction of drug concentration-time profiles in children from adults: an allometric approach
Iftekhar Mahmood1, Kosalaram Goteti
11Department of Hematology, Office of Blood Review & Research (OBRR), Center for Biologic Evaluation and Research, Food and Drug Administration, Rockville, MD; and 2Clinical Pharmacology and DMPK, MedImmune LLC, Gaithersburg, MD.
Abstract:
The main objective of this work was to evaluate 2 methods to predict concentration-time profiles of drugs in children (aged 5 years or older) from adult pharmacokinetic (PK) parameters. Five drugs from the literature were chosen for this study, and all these 5 drugs were described by a 2-compartment model in both adults and children. PK parameters (CL, Vc, Vss, and Vβ) were allometrically predicted in children from adults. PK constants such as A, B, α, and β were also predicted in children from adults as described in . Using predicted PK parameters and constants, concentration-time profiles of 5 drugs were predicted in children and compared with the observed profiles. Both methods of predictions provided fairly good prediction of concentration-time profiles in children. The predicted concentration-time profiles in children were comparable with the observed profiles and can be used to design first-in-children clinical trials.
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