Clindamycin Pharmacokinetics and Safety in Preterm and Term Infants
03/2016
Journal Article
Authors:
Gonzalez, D.;
Delmore, P.;
Bloom, B. T.;
Cotten, C. M.;
Poindexter, B. B.;
McGowan, E.;
Shattuck, K.;
Bradford, K. K. ;
Smith, P. B.;
Cohen-Wolkowiez, M.;
Morris, M.;
Yin, W.;
Benjamin, D. K., Jr.;
Laughon, M. M.
Volume:
60
Pagination:
2888-94
Issue:
5
Journal:
Antimicrob Agents Chemother
PMID:
26926644
URL:
https://www.ncbi.nlm.nih.gov/pubmed/26926644
Keywords:
Anti-Bacterial Agents/*pharmacokinetics Clindamycin/*pharmacokinetics Female Humans Infant Infant, Newborn Infant, Premature Microbial Sensitivity Tests Models, Theoretical Postmenopause Pregnancy Prospective Studies Staphylococcus aureus/drug effects
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 mug/ml in >90% of infants. There were no adverse events related to clindamycin use.
