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Use of Opportunistic Clinical Data and a Population Pharmacokinetic Model to Support Dosing of Clindamycin for Premature Infants to Adolescents
Author(s) -
Gonzalez D,
Melloni C,
Yogev R,
Poindexter B B,
Mendley S R,
Delmore P,
Sullivan J E,
Autmizguine J,
Lewandowski A,
Harper B,
Watt K M,
Lewis K C,
Capparelli E V,
Benjamin D K,
CohenWolkowiez M
Publication year - 2014
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2014.134
Subject(s) - dosing , nonmem , clindamycin , pharmacokinetics , medicine , population , body weight , pediatrics , antibiotics , pharmacology , chemistry , environmental health , biochemistry
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. Clinical Pharmacology & Therapeutics (2014); 96 4, 429–437. doi: 10.1038/clpt.2014.134