title: Clindamycin Pharmacokinetics and Safety in Preterm and Term Infants.
abstract: Clindamycin may be active against methicillin-resistant Staphylococcus aureus, a common pathogen causing sepsis in infants, but optimal dosing in this population is unknown. We performed a multicenter, prospective pharmacokinetic (PK) and safety study of clindamycin in infants. We analyzed the data using a population PK analysis approach and included samples from two additional pediatric trials. Intravenous data were collected from 62 infants (135 plasma PK samples) with postnatal ages of <121 days (median [range] gestational age of 28 weeks [23 to 42] and postnatal age of 17 days [1 to 115]). In addition to body weight, postmenstrual age (PMA) and plasma protein concentrations (albumin and alpha-1 acid glycoprotein) were found to be significantly associated with clearance and volume of distribution, respectively. Clearance reached 50% of the adult value at PMA of 39.5 weeks. Simulated PMA-based intravenous dosing regimens administered every 8 h (≤32 weeks PMA, 5 mg/kg; 32 to 40 weeks PMA, 7 mg/kg; >40 to 60 weeks PMA, 9 mg/kg) resulted in an unbound, steady-state concentration at half the dosing interval greater than a MIC for S. aureus of 0.12 μg/ml in >90% of infants. There were no adverse events related to clindamycin use. (This study has been registered at ClinicalTrials.gov under registration no. NCT01728363.).
authors.affiliation: Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gonzalez
authors.affiliation: Department of Neonatology, Wesley Medical Center, Wichita, Kansas, USA.
authors.forename: Paula
authors.initials: P
authors.lastname: Delmore
authors.affiliation: Department of Neonatology, Wesley Medical Center, Wichita, Kansas, USA.
authors.forename: Barry T
authors.initials: BT
authors.lastname: Bloom
authors.affiliation: Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA.
authors.forename: C Michael
authors.initials: CM
authors.lastname: Cotten
authors.affiliation: Department of Pediatrics, Riley Hospital for Children, Indiana University, Indianapolis, Indiana, USA.
authors.forename: Brenda B
authors.initials: BB
authors.lastname: Poindexter
authors.affiliation: Floating Hospital for Children at Tufts Medical Center, Boston, Massachusetts, USA.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: McGowan
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Shattuck
authors.affiliation: Department of Pediatrics, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Kathleen K
authors.initials: KK
authors.lastname: Bradford
authors.affiliation: Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
authors.forename: P Brian
authors.initials: PB
authors.lastname: Smith
authors.affiliation: Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Cohen-Wolkowiez
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
authors.forename: Maurine
authors.initials: M
authors.lastname: Morris
authors.affiliation: Emmes Corporation, Rockville, Maryland, USA.
authors.forename: Wanrong
authors.initials: W
authors.lastname: Yin
authors.affiliation: Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Benjamin
authors.affiliation: Department of Pediatrics, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA matt_laughon@med.unc.edu.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Laughon
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D002981:Clindamycin / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D008826:Microbial Sensitivity Tests; D008962:Models, Theoretical; D017698:Postmenopause; D011247:Pregnancy; D011446:Prospective Studies; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D002981:Clindamycin