Pharmacokinetics of Clindamycin in Obese and Nonobese Children

Antimicrob Agents Chemother. 2017 Mar 24;61(4):e02014-16. doi: 10.1128/AAC.02014-16. Print 2017 Apr.

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)0.75 × [PMA2.83/(39.52.83+PMA2.83)]; volume of distribution (V) was associated with TBW, albumin (ALB), and alpha-1 acid glycoprotein (AAG): V (liters) = 63.6 × (TBW/70) × (ALB/3.3)-0.83 × (AAG/2.4)-0.25 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.

Keywords: antibiotics; children; clindamycin; obesity; pharmacokinetics.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / pharmacokinetics*
  • Area Under Curve
  • Bayes Theorem
  • Biological Availability
  • Body Mass Index
  • Body Weight
  • Child
  • Clindamycin / blood
  • Clindamycin / pharmacokinetics*
  • Drug Administration Schedule
  • Drug Dosage Calculations
  • Female
  • Humans
  • Injections, Intravenous
  • Male
  • Models, Statistical*
  • Obesity / metabolism*
  • Obesity / physiopathology
  • Orosomucoid / metabolism
  • Serum Albumin / metabolism

Substances

  • Anti-Bacterial Agents
  • Orosomucoid
  • Serum Albumin
  • Clindamycin