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

Pharmacokinetics of Clindamycin in Obese and Nonobese Children

Michael J Smith  1   2 , Daniel Gonzalez  3 , Jennifer L Goldman  4 , Ram Yogev  5 , Janice E Sullivan  2 , Michael D Reed  6 , Ravinder Anand  7 , Karen Martz  7 , Katherine Berezny  8 , Daniel K Benjamin Jr  8   9 , P Brian Smith  8   9 , Michael Cohen-Wolkowiez  8   9 , Kevin Watt; Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee
Affiliations
Clinical Trial

Pharmacokinetics of Clindamycin in Obese and Nonobese Children

Michael J Smith et al. Antimicrob Agents Chemother. .

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.

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Figures

FIG 1
FIG 1
Clindamycin concentration versus time for merged data set of the Safety and Pharmacokinetics of Multiple-Dose Intravenous and Oral Clindamycin in Pediatric Subjects with BMI ≥ 85th Percentile (CLN01), Pharmacokinetics of Understudied Drugs Administered to Children per Standard of Care (POP01), and Pharmacokinetics of Antistaphylococcal Antibiotics in Infants (Staph Trio [STA01]) trials (A) and the CLN01 trial only (B).
FIG 2
FIG 2
Box plot of simulated total drug steady-state area under the curve (AUC) from 0 to 8 h following age-based clindamycin dosing and stratified by obesity status. Dosing was 12 mg/kg every 8 h for ages 2 to 6 years and 10 mg/kg every 8 h for ages >6 years, with a maximum dosage of 900 mg every 8 h. The upper and lower whiskers extend to the highest and lowest points that are within 1.5 times the interquartile range.
FIG 3
FIG 3
Box plot of simulated maximal drug concentration at steady state (Cmax,SS) following age-based clindamycin dosing and stratified by obesity status. Dosing was 12 mg/kg every 8 h for ages 2 to 6 years and 10 mg/kg every 8 h for ages >6 years, with a maximum dose of 900 mg every 8 h. The upper and lower whiskers extend to the highest and lowest points that are within 1.5 times the interquartile range.
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