Safety and Pharmacokinetics of Clindamycin in Pediatric Subjects With BMI ≥ 85th Percentile

Summary

The purpose of this study is to better understand how clindamycin works in children who fall in the 85th percentile or higher for body mass index (BMI - a ratio of weight to height). The results of the study will help better understand if children in higher BMI ranges process the medication differently and whether dosing should be adjusted in these children.

Timeline

Start

2013-06

Primary completion

2014-08

Completion

2014-08

Publications

• Background Gerber JS, Coffin SE, Smathers SA, Zaoutis TE. Trends in the incidence of methicillin-resistant Staphylococcus aureus infection in children's hospitals in the United States. Clin Infect Dis. 2009 Jul 1;49(1):65-71. doi: 10.1086/599348.
• Background Herigon JC, Hersh AL, Gerber JS, Zaoutis TE, Newland JG. Antibiotic management of Staphylococcus aureus infections in US children's hospitals, 1999-2008. Pediatrics. 2010 Jun;125(6):e1294-300. doi: 10.1542/peds.2009-2867. Epub 2010 May 17.
• Background Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of obesity and trends in body mass index among US children and adolescents, 1999-2010. JAMA. 2012 Feb 1;307(5):483-90. doi: 10.1001/jama.2012.40. Epub 2012 Jan 17.
• Background Kasten MJ. Clindamycin, metronidazole, and chloramphenicol. Mayo Clin Proc. 1999 Aug;74(8):825-33. doi: 10.4065/74.8.825.
• Background Pai MP, Bearden DT. Antimicrobial dosing considerations in obese adult patients. Pharmacotherapy. 2007 Aug;27(8):1081-91. doi: 10.1592/phco.27.8.1081.
• Background Bearden DT, Rodvold KA. Dosage adjustments for antibacterials in obese patients: applying clinical pharmacokinetics. Clin Pharmacokinet. 2000 May;38(5):415-26. doi: 10.2165/00003088-200038050-00003.
• Background Falagas ME, Kompoti M. Obesity and infection. Lancet Infect Dis. 2006 Jul;6(7):438-46. doi: 10.1016/S1473-3099(06)70523-0.
• Background Reed MD. Reversing the myths obstructing the determination of optimal age- and disease-based drug dosing in pediatrics. J Pediatr Pharmacol Ther. 2011 Jan;16(1):4-13.
• Background Jacobs MR. How can we predict bacterial eradication? Int J Infect Dis. 2003 Mar;7 Suppl 1:S13-20. doi: 10.1016/s1201-9712(03)90066-x.
• Background Bradley JS, Garonzik SM, Forrest A, Bhavnani SM. Pharmacokinetics, pharmacodynamics, and Monte Carlo simulation: selecting the best antimicrobial dose to treat an infection. Pediatr Infect Dis J. 2010 Nov;29(11):1043-6. doi: 10.1097/INF.0b013e3181f42a53. No abstract available.
• Background Bell MJ, Shackelford P, Smith R, Schroeder K. Pharmacokinetics of clindamycin phosphate in the first year of life. J Pediatr. 1984 Sep;105(3):482-6. doi: 10.1016/s0022-3476(84)80033-5.
• Background Koren G, Zarfin Y, Maresky D, Spiro TE, MacLeod SM. Pharmacokinetics of intravenous clindamycin in newborn infants. Pediatr Pharmacol (New York). 1986;5(4):287-92.
• Background DeHaan RM, Schellenberg D. Clindamycin palmitate flavored granules. Multidose tolerance, absorption, and urinary excretion study in healthy children. J Clin Pharmacol New Drugs. 1972 Feb-Mar;12(2):74-83. doi: 10.1002/j.1552-4604.1972.tb00149.x. No abstract available.
• Background DeHaan RM, Metzler CM, Schellenberg D, Vandenbosch WD. Pharmacokinetic studies of clindamycin phosphate. J Clin Pharmacol. 1973 May-Jun;13(5):190-209. doi: 10.1002/j.1552-4604.1973.tb00208.x. No abstract available.
• Background del Carmen Carrasco-Portugal M, Lujan M, Flores-Murrieta FJ. Evaluation of gender in the oral pharmacokinetics of clindamycin in humans. Biopharm Drug Dispos. 2008 Oct;29(7):427-30. doi: 10.1002/bdd.624.
• Background DeHaan RM, Metzler CM, Schellenberg D, VandenBosch WD, Masson EL. Pharmacokinetic studies of clindamycin hydrochloride in humans. Int J Clin Pharmacol. 1972 Jun;6(2):105-19. No abstract available.
• Background Townsend RJ, Baker RP. Pharmacokinetic comparison of three clindamycin phosphate dosing schedules. Drug Intell Clin Pharm. 1987 Mar;21(3):279-81. doi: 10.1177/106002808702100310.
• Background Wynalda MA, Hutzler JM, Koets MD, Podoll T, Wienkers LC. In vitro metabolism of clindamycin in human liver and intestinal microsomes. Drug Metab Dispos. 2003 Jul;31(7):878-87. doi: 10.1124/dmd.31.7.878.
• Background Green B, Duffull S. Caution when lean body weight is used as a size descriptor for obese subjects. Clin Pharmacol Ther. 2002 Dec;72(6):743-4. doi: 10.1067/mcp.2002.129306. No abstract available.
• Background Erstad BL. Which weight for weight-based dosage regimens in obese patients? Am J Health Syst Pharm. 2002 Nov 1;59(21):2105-10. doi: 10.1093/ajhp/59.21.2105. No abstract available.
• Background Weiss M. How does obesity affect residence time dispersion and the shape of drug disposition curves? Thiopental as an example. J Pharmacokinet Pharmacodyn. 2008 Jun;35(3):325-36. doi: 10.1007/s10928-008-9090-8. Epub 2008 May 9.
• Background Berezhkovskiy LM. On the accuracy of estimation of basic pharmacokinetic parameters by the traditional noncompartmental equations and the prediction of the steady-state volume of distribution in obese patients based upon data derived from normal subjects. J Pharm Sci. 2011 Jun;100(6):2482-97. doi: 10.1002/jps.22444. Epub 2011 Jan 19.
• Background Morrish GA, Pai MP, Green B. The effects of obesity on drug pharmacokinetics in humans. Expert Opin Drug Metab Toxicol. 2011 Jun;7(6):697-706. doi: 10.1517/17425255.2011.570331. Epub 2011 Mar 22.
• Background Leykin Y, Miotto L, Pellis T. Pharmacokinetic considerations in the obese. Best Pract Res Clin Anaesthesiol. 2011 Mar;25(1):27-36. doi: 10.1016/j.bpa.2010.12.002.
• Background Weinstein AJ, Gibbs RS, Gallagher M. Placental transfer of clindamycin and gentamicin in term pregnancy. Am J Obstet Gynecol. 1976 Apr 1;124(7):688-91. doi: 10.1016/s0002-9378(16)33336-1.
• Results 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 Jr, 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):429-37. doi: 10.1038/clpt.2014.134. Epub 2014 Jun 20.
• Results Gatti G, Flaherty J, Bubp J, White J, Borin M, Gambertoglio J. Comparative study of bioavailabilities and pharmacokinetics of clindamycin in healthy volunteers and patients with AIDS. Antimicrob Agents Chemother. 1993 May;37(5):1137-43. doi: 10.1128/AAC.37.5.1137.

Drugs

Indications