Expression ofIMPDHmRNA after Mycophenolate Administration in Male Volunteers

Abstract

Background. Mycophenolic acid (MPA) is the first-line antimetabolic immunosuppressants used in solid organ transplantation. Here,in vivoexpressions of the pharmacodynamic markerIMPDHmRNA were analyzed to investigate its usefulness in assessing drug effects.Materials and Methods. Six healthy male volunteers who had the same genotype for genes known to be associated with drug metabolism and effects were selected to remove the confounding effect of these genotypes. Mycophenolate mofetil (MMF, 1 g) was administered once to each subject, and blood samples were collected with certain interval before and after MMF administration to measure lymphocyte expression levels ofIMPDH1andIMPDH2mRNA. One week later, the experiment was repeated.Results. WhereasIMPDH1mRNA expression was stable,IMPDH2mRNA expression showed 2 peaks in the first week. BothIMPDH1andIMPDH2mRNA expression in the second week remarkably decreased from the first week.Conclusion. The temporary increase inIMPDH2mRNA expression in the first week might be due to a reactive reaction against the plasma MPA concentration. In the second week, the intracellular guanosine monophosphate might be depleted, renderingIMPDH2mRNA synthesis inactive. When MPA is regularly administered to reach a steady state, theIMPDH2mRNA expression may be kept low and may effectively reflect biological responses regardless of drug intake.