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.