Highly variable mycophenolate mofetil bioavailability following nonmyeloablative hematopoietic cell transplantation.
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.
Jacobson
Pamala
P
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.
Green
Kathleen
K
Rogosheske
John
J
Brunstein
Claudio
C
Ebeling
Breta
B
DeFor
Todd
T
McGlave
Philip
P
Weisdorf
Daniel
D
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
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003520:Cyclophosphamide; D014740:Vidarabine; D009173:Mycophenolic Acid; C024352:fludarabine