title: Use of opportunistic clinical data and a population pharmacokinetic model to support dosing of clindamycin for premature infants to adolescents.
abstract: Clindamycin is commonly prescribed to treat children with skin and skin-structure infections (including those caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA)), yet little is known about its pharmacokinetics (PK) across pediatric age groups. A population PK analysis was performed in NONMEM using samples collected in an opportunistic study from children receiving i.v. clindamycin per standard of care. The final model was used to optimize pediatric dosing to match adult exposure proven effective against CA-MRSA. A total of 194 plasma PK samples collected from 125 children were included in the analysis. A one-compartment model described the data well. The final model included body weight and a sigmoidal maturation relationship between postmenstrual age (PMA) and clearance (CL): CL (l/h) = 13.7 × (weight/70)(0.75) × (PMA(3.1)/(43.6(3.1) + PMA(3.1))); V (l) = 61.8 × (weight/70). Maturation reached 50% of adult CL values at ~44 weeks PMA. Our findings support age-based dosing.
authors.affiliation: 1] Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA [2] Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: D
authors.initials: D
authors.lastname: Gonzalez
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: C
authors.initials: C
authors.lastname: Melloni
authors.affiliation: Ann and Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors.forename: R
authors.initials: R
authors.lastname: Yogev
authors.affiliation: Department of Pediatrics, Riley Hospital for Children, Indiana University, Indianapolis, Indiana, USA.
authors.forename: B B
authors.initials: BB
authors.lastname: Poindexter
authors.affiliation: Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Mendley
authors.affiliation: Department of Pediatrics, Wesley Medical Center, Wichita, Kansas, USA.
authors.forename: P
authors.initials: P
authors.lastname: Delmore
authors.affiliation: Kosair Charities Pediatric Clinical Research Unit, Department of Pediatrics, University of Louisville, Louisville, Kentucky, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Sullivan
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: J
authors.initials: J
authors.lastname: Autmizguine
authors.affiliation: EMMES Corporation, Rockville, Maryland, USA.
authors.forename: A
authors.initials: A
authors.lastname: Lewandowski
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: B
authors.initials: B
authors.lastname: Harper
authors.affiliation: 1] Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA [2] Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Watt
authors.affiliation: OpAns, Durham, North Carolina, USA.
authors.forename: K C
authors.initials: KC
authors.lastname: Lewis
authors.affiliation: Department of Pediatrics, University of California, San Diego, California, USA.
authors.forename: E V
authors.initials: EV
authors.lastname: Capparelli
authors.affiliation: 1] Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA [2] Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: D K
authors.initials: DK
authors.lastname: Benjamin
authors.affiliation: 1] Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA [2] Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: M
authors.initials: M
authors.lastname: Cohen-Wolkowiez
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D002981:Clindamycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D008954:Models, Biological
chemical_list: D000900:Anti-Bacterial Agents; D002981:Clindamycin