Pharmacokinetics of Clindamycin in Obese and Nonobese Children.

Publication Type
Journal Article
Year of Publication
2017
Authors
Smith, Michael J; Gonzalez, Daniel; Goldman, Jennifer L; Yogev, Ram; Sullivan, Janice E; Reed, Michael D; Anand, Ravinder; Martz, Karen; Berezny, Katherine; Benjamin, Daniel K; Smith, P Brian; Cohen-Wolkowiez, Michael; Watt, Kevin; Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee
Secondary
Antimicrob Agents Chemother
Volume
61
Date Published
2017 04
Keywords
Adolescent; Anti-Bacterial Agents; Area Under Curve; Bayes Theorem; Biological Availability; body mass index; Body Weight; Child; Clindamycin; Drug Administration Schedule; Drug Dosage Calculations; Female; Humans; Injections, Intravenous; Male; Models, Statistical; obesity; Orosomucoid; Serum Albumin
Abstract

Although obesity is prevalent among children in the United States, pharmacokinetic (PK) data for obese children are limited. Clindamycin is a commonly used antibiotic that may require dose adjustment in obese children due to its lipophilic properties. We performed a clindamycin population PK analysis using data from three separate trials. A total of 420 samples from 220 children, 76 of whom had a body mass index greater than or equal to the 95th percentile for age, were included in the analysis. Compared to other metrics, total body weight (TBW) was the most robust measure of body size. The final model included TBW and a sigmoidal maturation relationship between postmenstrual age (PMA) and clearance (CL): CL (liters/hour) = 13.8 × (TBW/70) × [PMA/(39.5+PMA)]; volume of distribution () was associated with TBW, albumin (ALB), and alpha-1 acid glycoprotein (AAG): (liters) = 63.6 × (TBW/70) × (ALB/3.3) × (AAG/2.4) After accounting for differences in TBW, obesity status did not explain additional interindividual variability in model parameters. Our findings support TBW-based dosing for obese and nonobese children.