title: Pharmacokinetics of mycophenolate mofetil in hematopoietic stem cell transplant recipients.
abstract: Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), is increasingly used in the prophylaxis of graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HCT). Few pharmacokinetic data are available about the use of MMF for this indication. This case series aimed at analyzing the pharmacokinetics of MMF in a population of HCT recipients representative for everyday practice. From 15 HCT recipients, serial plasma samples were taken after twice-daily oral intake of MMF. Plasma concentrations of total MPA and its glucuronide metabolites, as well as free MPA, were quantified. Median apparent oral MPA clearance (CL/F), apparent half-life, and total MPA area under the curve for hours 0 to 12 (AUC0-12, normalized to 1000 mg MMF) were, respectively, 56 L/h (range: 29-98 L/h), 2.3 hours (range: 0.8-5.7 hours), and 18.0 mg*h/L (range: 10-35 mg*h/L). Total MPA concentrations were below 2 mg/L 8 hours after MMF administration, indicating reduced enterohepatic recirculation. Median free MPA AUC0-12 (normalized to 1000 mg MMF) was 224 microg*h/L (range: 56-411 microg*h/L). Because of high CL/F, total MPA exposure in HCT recipients is low and apparent half-life is short in comparison with reference values from renal transplantation. Exposure may be improved in HCT recipients by higher or more frequent MMF dosing.
authors.affiliation: Department of Hospital Pharmacy (Clinical Pharmacology Unit), Erasmus MC, Rotterdam, The Netherlands. r.vanhest@erasmusmc.nl
authors.forename: Reinier M
authors.initials: RM
authors.lastname: van Hest
authors.forename: Jeanette K
authors.initials: JK
authors.lastname: Doorduijn
authors.forename: Brenda C M
authors.initials: BC
authors.lastname: de Winter
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Cornelissen
authors.forename: Arnold G
authors.initials: AG
authors.lastname: Vulto
authors.forename: Michael
authors.initials: M
authors.lastname: Oellerich
authors.forename: Bob
authors.initials: B
authors.lastname: Löwenberg
authors.forename: Ron A A
authors.initials: RA
authors.lastname: Mathot
authors.forename: Victor William
authors.initials: VW
authors.lastname: Armstrong
authors.forename: Teun
authors.initials: T
authors.lastname: van Gelder
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006207:Half-Life; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid