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

Publication ,  Journal Article
Gonzalez, D; Melloni, C; Yogev, R; Poindexter, BB; Mendley, SR; Delmore, P; Sullivan, JE; Autmizguine, J; Lewandowski, A; Harper, B; Watt, KM ...
Published in: Clin Pharmacol Ther
October 2014

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.

Duke Scholars

Published In

Clin Pharmacol Ther

DOI

EISSN

1532-6535

Publication Date

October 2014

Volume

96

Issue

4

Start / End Page

429 / 437

Location

United States

Related Subject Headings

  • Pharmacology & Pharmacy
  • Models, Biological
  • Male
  • Infant, Premature
  • Infant, Newborn
  • Infant
  • Humans
  • Female
  • Dose-Response Relationship, Drug
  • Clindamycin
 

Citation

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Gonzalez, D., Melloni, C., Yogev, R., Poindexter, B. B., Mendley, S. R., Delmore, P., … Best Pharmaceuticals for Children Act – Pediatric Trials Network Administrative Core Committee, . (2014). Use of opportunistic clinical data and a population pharmacokinetic model to support dosing of clindamycin for premature infants to adolescents. Clin Pharmacol Ther, 96(4), 429–437. https://doi.org/10.1038/clpt.2014.134
Gonzalez, D., C. Melloni, R. Yogev, B. B. Poindexter, S. R. Mendley, P. Delmore, J. E. Sullivan, et al. “Use of opportunistic clinical data and a population pharmacokinetic model to support dosing of clindamycin for premature infants to adolescents.Clin Pharmacol Ther 96, no. 4 (October 2014): 429–37. https://doi.org/10.1038/clpt.2014.134.
Gonzalez D, Melloni C, Yogev R, Poindexter BB, Mendley SR, Delmore P, et al. Use of opportunistic clinical data and a population pharmacokinetic model to support dosing of clindamycin for premature infants to adolescents. Clin Pharmacol Ther. 2014 Oct;96(4):429–37.
Gonzalez, D., et al. “Use of opportunistic clinical data and a population pharmacokinetic model to support dosing of clindamycin for premature infants to adolescents.Clin Pharmacol Ther, vol. 96, no. 4, Oct. 2014, pp. 429–37. Pubmed, doi:10.1038/clpt.2014.134.
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, Best Pharmaceuticals for Children Act – Pediatric Trials Network Administrative Core Committee. Use of opportunistic clinical data and a population pharmacokinetic model to support dosing of clindamycin for premature infants to adolescents. Clin Pharmacol Ther. 2014 Oct;96(4):429–437.
Journal cover image

Published In

Clin Pharmacol Ther

DOI

EISSN

1532-6535

Publication Date

October 2014

Volume

96

Issue

4

Start / End Page

429 / 437

Location

United States

Related Subject Headings

  • Pharmacology & Pharmacy
  • Models, Biological
  • Male
  • Infant, Premature
  • Infant, Newborn
  • Infant
  • Humans
  • Female
  • Dose-Response Relationship, Drug
  • Clindamycin