Pharmacokinetics of clindamycin in obese and nonobese children

Michael J. Smith; Daniel Gonzalez; Jennifer L. Goldman; Ram Yogev; Janice E. Sullivan; Michael D. Reed; Ravinder Anand; Karen Martz; Katherine Berezny; Daniel K. Benjamin; P. Brian Smith; Michael Cohen-Wolkowiez; Kevin Watt

doi:10.1128/AAC.02014-16

Pharmacokinetics of clindamycin in obese and nonobese children

Michael J. Smith^*, Daniel Gonzalez, Jennifer L. Goldman, Ram Yogev, Janice E. Sullivan, Michael D. Reed, Ravinder Anand, Karen Martz, Katherine Berezny, Daniel K. Benjamin, P. Brian Smith, Michael Cohen-Wolkowiez, Kevin Watt

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

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 × [PMA^2.83/(39.5^2.83+PMA^2.83)]; 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.

Original language	English (US)
Article number	e02014-16
Journal	Antimicrobial agents and chemotherapy
Volume	61
Issue number	4
DOIs	https://doi.org/10.1128/AAC.02014-16
State	Published - Apr 2017

Keywords

Antibiotics
Children
Clindamycin
Obesity
Pharmacokinetics

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1128/AAC.02014-16

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@article{872882fb1df848a6a447112ddab5ded5,

title = "Pharmacokinetics of clindamycin in obese and nonobese children",

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",

author = "Smith, {Michael J.} and Daniel Gonzalez and Goldman, {Jennifer L.} and Ram Yogev and Sullivan, {Janice E.} and Reed, {Michael D.} and Ravinder Anand and Karen Martz and Katherine Berezny and Benjamin, {Daniel K.} and Smith, {P. Brian} and Michael Cohen-Wolkowiez and Kevin Watt",

note = "Funding Information: This work was funded under National Institute of Child Health and Human Development (NICHD) contract HHSN27500018 (Kevin Watt) for the Safety and Pharmaco- kinetics of Multiple-Dose Intravenous and Oral Clindamycin in Pediatric Subjects with BMI = 85th Percentile study (protocol NICHD-2012-CLN01). Research reported in this publication was also supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) under award number UL1TR001117. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Daniel Gonzalez is funded by K23HD083465 from the National Institute for Child Health and Human Development (NICHD) and by the nonprofit Thrasher Research Fund (https://www.thrasherresearch.org). Publisher Copyright: Copyright {\textcopyright} 2017 American Society for Microbiology.",

year = "2017",

month = apr,

doi = "10.1128/AAC.02014-16",

language = "English (US)",

volume = "61",

journal = "Antimicrobial Agents and Chemotherapy",

issn = "0066-4804",

publisher = "American Society for Microbiology",

number = "4",

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T1 - Pharmacokinetics of clindamycin in obese and nonobese children

AU - Smith, Michael J.

AU - Gonzalez, Daniel

AU - Goldman, Jennifer L.

AU - Yogev, Ram

AU - Sullivan, Janice E.

AU - Reed, Michael D.

AU - Anand, Ravinder

AU - Martz, Karen

AU - Berezny, Katherine

AU - Benjamin, Daniel K.

AU - Smith, P. Brian

AU - Cohen-Wolkowiez, Michael

AU - Watt, Kevin

N1 - Funding Information: This work was funded under National Institute of Child Health and Human Development (NICHD) contract HHSN27500018 (Kevin Watt) for the Safety and Pharmaco- kinetics of Multiple-Dose Intravenous and Oral Clindamycin in Pediatric Subjects with BMI = 85th Percentile study (protocol NICHD-2012-CLN01). Research reported in this publication was also supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) under award number UL1TR001117. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Daniel Gonzalez is funded by K23HD083465 from the National Institute for Child Health and Human Development (NICHD) and by the nonprofit Thrasher Research Fund (https://www.thrasherresearch.org). Publisher Copyright: Copyright © 2017 American Society for Microbiology.

PY - 2017/4

Y1 - 2017/4

N2 - 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.

AB - 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.

KW - Antibiotics

KW - Children

KW - Clindamycin

KW - Obesity

KW - Pharmacokinetics

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VL - 61

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

IS - 4

M1 - e02014-16

ER -

Pharmacokinetics of clindamycin in obese and nonobese children

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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