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Inosine monophosphate dehydrogenase activity in paediatrics: age-related regulation and response to mycophenolic acid

A Rother1, P Glander, E Vitt

  • 1Department of Paediatrics I, University Children's Hospital Heidelberg, Heidelberg, Germany.

European Journal of Clinical Pharmacology
|January 26, 2012
PubMed

Insights

Inosine 5'-monophosphate dehydrogenase (IMPDH) activity shows high variability but no significant developmental regulation in children and adolescents. MPA effectively inhibits IMPDH in pediatric renal transplant recipients, similar to adults.

Area of Science:

  • Pharmacology
  • Biochemistry
  • Pediatrics

Background:

  • Drug targets and metabolizing enzymes can be developmentally regulated.
  • Inosine 5 omino-monophosphate dehydrogenase (IMPDH) activity is a potential biomarker for mycophenolic acid (MPA) effects.
  • Monitoring MPA pharmacodynamics in pediatric populations is evolving.

Purpose of the Study:

  • To investigate developmental regulation of IMPDH activity in pediatric populations.
  • To analyze MPA's effect on IMPDH activity in children versus adolescents post-renal transplantation.

Main Methods:

  • IMPDH activity was measured in peripheral blood mononuclear cells (PBMCs) from 79 healthy children (2.0-17.9 years) and 106 healthy adults.
  • Pharmacokinetic/pharmacodynamic profiles of MPA and IMPDH were assessed in 17 pediatric renal transplant recipients.
  • IMPDH activity was measured by HPLC and normalized to AMP content; MPA plasma concentrations were determined by HPLC.

Main Results:

  • IMPDH activity exhibited high inter-individual variability (40.2% CV) across all ages studied.
  • Median IMPDH activity did not significantly differ between healthy children, adolescents, and adults.
  • IMPDH activity in children and adolescents was inversely correlated with MPA plasma concentration, similar to adults.

Conclusions:

  • The study found no pronounced developmental regulation of IMPDH activity in the pediatric population.
  • MPA demonstrated comparable inhibition of IMPDH activity in pediatric renal transplant recipients (children and adolescents) compared to adults.
Abstract

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