Use of opportunistic clinical data and a population pharmacokinetic model to support dosing of clindamycin for premature infants to adolescents

D. Gonzalez, C. Melloni, R. Yogev, B. B. Poindexter, S. R. Mendley, P. Delmore, J. E. Sullivan, J. Autmizguine, A. Lewandowski, B. Harper, K. M. Watt, K. C. Lewis, E. V. Capparelli, D. K. Benjamin, M. Cohen-Wolkowiez

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)429-437
Number of pages9
JournalClinical Pharmacology and Therapeutics
Volume96
Issue number4
DOIs
StatePublished - Oct 1 2014

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Clindamycin
Premature Infants
Pharmacokinetics
Methicillin-Resistant Staphylococcus aureus
Pediatrics
Population
Weights and Measures
Skin
Standard of Care
Age Groups
Body Weight
Infection

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Use of opportunistic clinical data and a population pharmacokinetic model to support dosing of clindamycin for premature infants to adolescents. / 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.; Cohen-Wolkowiez, M.

In: Clinical Pharmacology and Therapeutics, Vol. 96, No. 4, 01.10.2014, p. 429-437.

Research output: Contribution to journalArticle

Gonzalez, D, Melloni, C, Yogev, R, Poindexter, BB, Mendley, SR, Delmore, P, Sullivan, JE, Autmizguine, J, Lewandowski, A, Harper, B, Watt, KM, Lewis, KC, Capparelli, EV, Benjamin, DK & Cohen-Wolkowiez, M 2014, 'Use of opportunistic clinical data and a population pharmacokinetic model to support dosing of clindamycin for premature infants to adolescents', Clinical Pharmacology and Therapeutics, vol. 96, no. 4, pp. 429-437. https://doi.org/10.1038/clpt.2014.134
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. ; Cohen-Wolkowiez, M. / Use of opportunistic clinical data and a population pharmacokinetic model to support dosing of clindamycin for premature infants to adolescents. In: Clinical Pharmacology and Therapeutics. 2014 ; Vol. 96, No. 4. pp. 429-437.
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