European Journal of Clinical Pharmacology

, Volume 68, Issue 6, pp 913–922

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

  • A. Rother
  • P. Glander
  • E. Vitt
  • D. Czock
  • N. von Ahsen
  • V. W. Armstrong
  • M. Oellerich
  • K. Budde
  • R. Feneberg
  • B. Tönshoff
  • L. T. Weber



Since many drug targets and metabolizing enzymes are developmentally regulated, we investigated a potential comparable regulation of inosine 5’-monophosphate dehydrogenase (IMPDH) activity that has recently been advocated as a pharmacodynamic biomarker of mycophenolic acid (MPA) effects in the paediatric population. Since the field of pharmacodynamic monitoring of MPA is evolving, we also analyzed the response of IMPDH activity on MPA in children vs adolescents after renal transplantation.


We analyzed IMPDH activity in peripheral blood mononuclear cells (PBMCs) in 79 healthy children aged 2.0–17.9 years in comparison to 106 healthy adults. Pharmacokinetic/pharmacodynamic profiles of MPA and IMPDH over 6 or 12 h after mycophenolate mofetil dosing were performed in 17 paediatric renal transplant recipients. IMPDH activity was measured by HPLC and normalized to the adenosine monophosphate (AMP) content of the cells, MPA plasma concentrations were measured by HPLC.


Inosine 5’-monophosphate dehydrogenase activity displayed a high inter-individual variability (coefficient of variation 40.2%) throughout the entire age range studied. Median IMPDH did not differ significantly in healthy pre-school children (82 [range, 42–184] μmol/s/mol AMP), school-age children (61 [30–153]), adolescents (83 [43–154]) and healthy adults (83 [26–215]). Similar to adults, IMPDH activity in children and adolescents was inversely correlated with MPA plasma concentration.


In conclusion, our data do not show a pronounced developmental regulation of IMPDH activity in PBMCs in the paediatric population and there is a comparable inhibition of IMPDH activity by MPA in children and adolescents after renal transplantation.


IMPDH activity Developmental regulation Pharmacodynamics Paediatric renal transplantation Mycophenolic acid 



IMPDH activity


Area under the enzyme activity–time curve


Akaike information criterion


Maximal possible IMPDH inhibition


Minimum IMPDH activity


Adenosine monophosphate


Analysis of variance


Area under the concentration–time curve


Body surface area


Body mass index standard deviation score


MPA concentration


Apparent drug clearance


Maximum MPA concentration


Administered MPA content


End-stage renal disease




Sigmoidicity parameter


High-performance liquid chromatography


Inosine 5’-monophosphate dehydrogenase


Mycophenolic acid


Mycophenolate mofetil


Peripheral blood mononuclear cells






Renal transplantation


Standard deviation


Single nucleotide polymorphism


Time to minimum IMPDH activity


Time of maximum MPA concentration in a dosing interval


Xanthosine 5’-monophosphate


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • A. Rother
    • 1
  • P. Glander
    • 2
  • E. Vitt
    • 3
  • D. Czock
    • 4
  • N. von Ahsen
    • 5
  • V. W. Armstrong
    • 5
  • M. Oellerich
    • 5
  • K. Budde
    • 2
  • R. Feneberg
    • 1
  • B. Tönshoff
    • 1
  • L. T. Weber
    • 3
    • 6
  1. 1.Department of Paediatrics IUniversity Children’s Hospital HeidelbergHeidelbergGermany
  2. 2.Department of NephrologyCharité Universitätsmedizin BerlinBerlinGermany
  3. 3.Department of Paediatric NephrologyChildren’s Hospital of the Ludwig-Maximilians University of MunichMunichGermany
  4. 4.Department of Clinical Pharmacology and PharmacoepidemiologyUniversity Hospital HeidelbergHeidelbergGermany
  5. 5.Department of Clinical ChemistryUniversity of GöttingenGöttingenGermany
  6. 6.Paediatric NephrologyUniversity Children’s Hospital, Dr. von Haunersche KinderklinikMunichGermany

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