title: Plasma concentrations of mycophenolic acid acyl glucuronide are not associated with diarrhea in renal transplant recipients.
abstract: The aim of this study was to determine whether plasma concentrations of the acyl (AcMPAG) and phenolic (MPAG) glucuronide metabolites of mycophenolic acid (MPA) were related to diarrhoea in renal transplant patients on mycophenolate mofetil (MMF) with cyclosporine (CsA) or tacrolimus (TCL). Blood samples (0, 30, 120 min) were taken at days 3, 10, week 4, months 3, 6 and 12 for determination of MPA, MPAG and AcMPAG. MPA-AUC was estimated using validated algorithms. Two hour AUCs were calculated for MPAG and AcMPAG. Immunosuppressive therapy consisted of CsA/MMF (n= 110) and of TCL/MMF (n= 180). In 70/290 (24%) patients 86 episodes of diarrhoea were recorded during 12 months. Significantly more patients on TCL (31.1%) suffered from diarrhea compared to CsA (12.7%). MMF dose, MPA-AUC and the 2 h AUCs of MPAG and AcMPAG did not differ between patients with and without diarrhoea. Plasma AcMPAG and MPAG concentrations were substantially higher in patients on CsA compared with TCL, while MPA-AUC was lower in the former group. These data support the concept that CsA inhibits the biliary excretion of MPAG and AcMPAG, thereby potentially reducing the risk of intestinal injury through enterohepatic recycling of MPA and its metabolites.
authors.affiliation: Department of Clinical Chemistry, Georg-August-Universität Göttingen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Heller
authors.forename: T
authors.initials: T
authors.lastname: van Gelder
authors.forename: K
authors.initials: K
authors.lastname: Budde
authors.forename: J W
authors.initials: JW
authors.lastname: de Fijter
authors.forename: D
authors.initials: D
authors.lastname: Kuypers
authors.forename: W
authors.initials: W
authors.lastname: Arns
authors.forename: J
authors.initials: J
authors.lastname: Schmidt
authors.forename: L
authors.initials: L
authors.lastname: Rostaing
authors.forename: S H
authors.initials: SH
authors.lastname: Powis
authors.forename: K
authors.initials: K
authors.lastname: Claesson
authors.forename: I A M
authors.initials: IA
authors.lastname: Macphee
authors.forename: E
authors.initials: E
authors.lastname: Pohanka
authors.forename: J
authors.initials: J
authors.lastname: Engelmayer
authors.forename: G
authors.initials: G
authors.lastname: Brandhorst
authors.forename: M
authors.initials: M
authors.lastname: Oellerich
authors.forename: V W
authors.initials: VW
authors.lastname: Armstrong
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D016572:Cyclosporine / Q000627:therapeutic use; D003967:Diarrhea / Q000139:chemically induced* / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D020719:Glucuronides / Q000009:adverse effects* / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000097:blood; D015994:Incidence; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D016019:Survival Analysis; D016559:Tacrolimus / Q000627:therapeutic use
chemical_list: D000305:Adrenal Cortex Hormones; D020719:Glucuronides; D007166:Immunosuppressive Agents; C113145:mycophenolic acid glucuronide; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus