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)-0.25After 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.
authors.affiliation: Division of Pediatric Infectious Diseases, University of Louisville, Louisville, Kentucky, USA mjsmit22@louisville.edu.|Kosair Charities Pediatric Clinical Research Unit, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Smith
authors.affiliation: Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gonzalez
authors.affiliation: Children's Mercy Hospital, Kansas City, Missouri, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Goldman
authors.affiliation: Northwestern University, Chicago, Illinois, USA.
authors.forename: Ram
authors.initials: R
authors.lastname: Yogev
authors.affiliation: Kosair Charities Pediatric Clinical Research Unit, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Janice E
authors.initials: JE
authors.lastname: Sullivan
authors.affiliation: Akron Children's Hospital, Akron, Ohio, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Reed
authors.affiliation: EMMES Corp., Rockville, Maryland, USA.
authors.forename: Ravinder
authors.initials: R
authors.lastname: Anand
authors.affiliation: EMMES Corp., Rockville, Maryland, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Martz
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Berezny
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.|Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Benjamin
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.|Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA.
authors.forename: P Brian
authors.initials: PB
authors.lastname: Smith
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.|Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Cohen-Wolkowiez
authors.forename: Kevin
authors.initials: K
authors.lastname: Watt
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001499:Bayes Theorem; D001682:Biological Availability; D015992:Body Mass Index; D001835:Body Weight; D002648:Child; D002981:Clindamycin / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D015233:Models, Statistical; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D009961:Orosomucoid / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D009961:Orosomucoid; D012709:Serum Albumin; D002981:Clindamycin
keywords: antibiotics; children; clindamycin; obesity; pharmacokinetics