title: Prediction of glucuronidated drug clearance in pediatrics (≤5 years): An allometric approach.
abstract: Children are not small adults. The differences between children of different age groups and adults are not merely due to body weight, but also due to physiological and biochemical differences resulting in different rates of drug metabolism or renal clearance. Glucuronidation is an important pathway of drug metabolism. Therefore, the objective of this study is to evaluate the predictive performance of several allometric exponents in children of ≤5 years for the total clearance of drugs which are mainly metabolized by glucuronidation. Four exponents (0.75, 1.0, 1.2, or 1.4) on the body weights and an allometric model developed from adults were evaluated. The four exponents and the allometric model were examined to determine the suitability of the method(s) to predict the clearances of drugs which are glucuronidated in children ≤5 years of age. Based on the analysis of ten drugs, it was noted that the combination of two allometric exponents 1.2 (for children ≤3 months) and 1.0 (for children ≥3 months ≤5 years) can be used to predict mean clearances of drugs which are mainly metabolized by glucuronidation. The suggested approach may be used to estimate a first-in-pediatric dose to initiate a pediatric clinical trial.
authors: Division of Hematology, Office of Blood Review and Research (OBRR), Center for Biologic Evaluation and Research, Food and Drug Administration, 1401, Rockville Pike, Rockville, MD, 20852, USA, iftekhar.mahmood@fda.hhs.gov.
authors: Iftekhar
authors: I
authors: Mahmood
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001711:Biotransformation; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D054796:Drug Dosage Calculations; D005260:Female; D005865:Gestational Age; D020719:Glucuronides / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*; D015203:Reproducibility of Results; D047929:Term Birth; D055815:Young Adult
chemical_list: D020719:Glucuronides; D004364:Pharmaceutical Preparations