4.7 Article

Pharmacokinetics of Clindamycin in Obese and Nonobese Children

期刊

出版社

AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.02014-16

关键词

clindamycin; pharmacokinetics; children; obesity; antibiotics

资金

  1. National Institute of Child Health and Human Development (NICHD) [HHSN27500018]
  2. National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) [UL1TR001117]
  3. National Institute for Child Health and Human Development (NICHD) [K23HD083465, HHSN275201000003I, 1R01-HD081044-01]
  4. nonprofit Thrasher Research Fund
  5. National Institutes of Health (NIH) [2K24HD058735-06, 1R01-HD076676-01A1]
  6. National Center for Advancing Translational Sciences [UL1TR001117]
  7. Cempra Pharmaceuticals and industry for neonatal and pediatric drug development [HHSO100201300009C]
  8. National Center for Advancing Translational Sciences of the NIH [UL1TR001117]
  9. Food and Drug Administration (FDA) [1R18-FD00529201]
  10. Shionogi and industry for neonatal and pediatric drug development
  11. NIAID [HHSN272201500006I, HHSN272201300017I]
  12. NICHD [HHSN275201000003I, 1K23HD075891, 5K12HD047349]
  13. FDA [1U01FD004858-01]
  14. Biomedical Advanced Research and Development Authority [HHSO100201300009C]
  15. industry (CardioDx and Durata Therapeutics) for drug development in adults and children

向作者/读者索取更多资源

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 X (TBW/70)(0.75) X [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 X (TBW/ 70) X (ALB/ 3.3)(-0.83) X (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.

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