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 Jr, M Cohen-Wolkowiez, Best Pharmaceuticals for Children Act – Pediatric Trials Network Administrative Core Committee, Katherine Y Berezny, Jeffrey Barrett, Gregory L Kearns, Matthew Laughon, Andre Muelenaer, T Michael O'Shea, Winston Salem, Ian M Paul, P Brian Smith, John van den Anker, Kelly Wade, Thomas J Walsh, David Siegel, Perdita Taylor-Zapata, Anne Zajicek, Zhaoxia Ren, Alice Pagan, Ravinder Anand, Traci Clemons, Gina Simone, Andrew Lewandowski, Barrie Harper, Ram Yogev, Laura Fern, Brenda Poindexter, Lucy Smiley, Susan Mendley, Donna Cannonier, Paula Delmore, Janice Sullivan, Tressa Bratton, 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 Jr, M Cohen-Wolkowiez, Best Pharmaceuticals for Children Act – Pediatric Trials Network Administrative Core Committee, Katherine Y Berezny, Jeffrey Barrett, Gregory L Kearns, Matthew Laughon, Andre Muelenaer, T Michael O'Shea, Winston Salem, Ian M Paul, P Brian Smith, John van den Anker, Kelly Wade, Thomas J Walsh, David Siegel, Perdita Taylor-Zapata, Anne Zajicek, Zhaoxia Ren, Alice Pagan, Ravinder Anand, Traci Clemons, Gina Simone, Andrew Lewandowski, Barrie Harper, Ram Yogev, Laura Fern, Brenda Poindexter, Lucy Smiley, Susan Mendley, Donna Cannonier, Paula Delmore, Janice Sullivan, Tressa Bratton
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.
Conflict of interest statement
Conflict-of-Interest Disclosures
D.G. is funded by training grant T32GM086330 from the National Institute of General Medical Sciences (NIGMS). K.M.W. receives support from NIGMS (1T32GM086330-01A1) and the Thrasher Research Fund (www.thrasherresearch.org) for his work in pediatric clinical pharmacology. E.V.C. receives salary support from the United States government (U54 HD071600-01) and research support from Trius, Cerexa Pharmaceuticals, Abbott, and Theravance. D.K.B. Jr. receives support from the United States government for his work in pediatric and neonatal clinical pharmacology (1R01HD057956-05, 1K24HD058735-05, UL1TR001117, and NICHD contract HHSN275201000003I) and the nonprofit organization Thrasher Research Fund for his work in neonatal candidiasis (www.thrasherresearch.org); he also receives research support from industry for neonatal and pediatric drug development (www.dcri.duke.edu/research/coi.jsp). M.C.W. receives support for research from the NIH (1K23HD064814), the National Center for Advancing Translational Sciences of the NIH (UL1TR001117), the Food and Drug Administration (1U01FD004858-01), the Biomedical Advanced Research and Development Authority (BARDA) (HHSO100201300009C), the nonprofit organization Thrasher Research Fund (www.thrasherresearch.org), and from industry for drug development in adults and children (www.dcri.duke.edu/research/coi.jsp). The remaining authors have no funding to disclose.
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Source: PubMed