title: Highly variable mycophenolate mofetil bioavailability following nonmyeloablative hematopoietic cell transplantation.
abstract: This study determined the oral bioavailability of mycophenolic acid, the active metabolite of mycophenolate mofetil, in patients undergoing nonmyeloablative hematopoietic cell transplantation. Eighteen adults receiving a preparative regimen containing fludarabine, cyclophosphamide, and total body irradiation were studied. Immune suppression consisted of cyclosporine and mycophenolate 1 g twice daily. Pharmacokinetic variability was high after intravenous and oral dosing. Intravenous dosing resulted in a median area under the curve (AUC) of 28.3 microg x h/mL (range, 9.96-70.4) and an oral AUC of 16.7 microg x h/mL (range, 9.38-35.3). Cmax after intravenous and oral dosing was 12.18 and 5.29 microg/mL, respectively. The median oral bioavailability was 72.3% (20.5%-172%), with 8-fold variability. Five patients (28%) had an oral bioavailability < or = 50%. At time of oral pharmacokinetics, 15 patients (83%) had an AUC(0-12) < 30 microg x h/mL. The initial oral dose should be at least 25% greater than the intravenous dose with follow-up assessment of plasma concentrations.
authors.affiliation: Department of Experimental and Clinical Pharmacology, Weaver Densford Hall 7-189, 308 Harvard Street SE, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Pamala
authors.initials: P
authors.lastname: Jacobson
authors.forename: Kathleen
authors.initials: K
authors.lastname: Green
authors.forename: John
authors.initials: J
authors.lastname: Rogosheske
authors.forename: Claudio
authors.initials: C
authors.lastname: Brunstein
authors.forename: Breta
authors.initials: B
authors.lastname: Ebeling
authors.forename: Todd
authors.initials: T
authors.lastname: DeFor
authors.forename: Philip
authors.initials: P
authors.lastname: McGlave
authors.forename: Daniel
authors.initials: D
authors.lastname: Weisdorf
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001682:Biological Availability; D003520:Cyclophosphamide / Q000008:administration & dosage; D016572:Cyclosporine / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D018709:Statistics, Nonparametric; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014916:Whole-Body Irradiation
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003520:Cyclophosphamide; D014740:Vidarabine; D009173:Mycophenolic Acid; C024352:fludarabine