Meropenem pharmacokinetics in children and adolescents receiving hemodialysis

Pediatr Nephrol. 2001 Dec;16(12):1015-8. doi: 10.1007/s004670100015.

Abstract

The emergence of multi-drug-resistant bacteria is of great concern to the care of pediatric end-stage renal disease (ESRD) patients who receive either hemodialysis or peritoneal dialysis via a catheter. Infections with gram-negative organisms, especially Pseudomonas aeruginosa, are difficult to eradicate and often necessitate catheter removal. Meropenem, a broad-spectrum antibiotic of the carbapenem class of beta-lactams, is effective against most gram-positive and gram-negative bacteria and has enhanced activity against P. aeruginosa. We studied the pharmacokinetics of meropenem during and between hemodialysis treatments in seven pediatric patients. Meropenem was given as a single dose of 20 mg/kg (maximum 500 mg) before and after two separate hemodialysis treatments. Meropenem administration was tolerated without any adverse effects. Hemodialysis effectively cleared meropenem in a manner that correlated with percent urea reduction. Median drug half-life was 7.3 h off dialysis (range 4.9-11.7 h). The dose of 20 mg/kg was not sufficient to produce an acceptable interdialytic pharmacodynamic profile of 70% duration with a meropenem concentration >4 microg/ml, the MIC90 of meropenem for P. aeruginosa. Dosing simulations revealed that a daily dose of 25 mg/kg or an alternate day dose of 40 mg/kg would result in an acceptable pharmacodynamic profile. Both simulated doses achieved acceptable peak concentrations.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Computer Simulation
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Infant
  • Kidney Failure, Chronic / metabolism*
  • Kidney Failure, Chronic / therapy*
  • Male
  • Meropenem
  • Models, Theoretical
  • Renal Dialysis*
  • Thienamycins / administration & dosage
  • Thienamycins / pharmacokinetics*

Substances

  • Thienamycins
  • Meropenem