The aim of this prospective study was to characterize the multiple-dose pharmacokinetics of mycophenolic acid (MPA) after administration of a 3-hour intravenous (IV) infusion of mycophenolate mofetil (MMF, CellCept) at a dose level of 1.5 g every 12 hours for 5 full days to cardiac allograft recipients and to compare the bioavailability of MPA after a switch from the IV infusion to an oral dose of 1.5 g every 12 hours from day 6. In addition to MMF, patients received cyclosporine and prednisolone. Blood (EDTA) samples for full pharmacokinetic profiles were obtained for 9 patients on days 3 and 5 (IV MMF) and on days 6 and 10 (oral MMF). They were centrifuged within 45 minutes of collection, and plasma was stabilized by addition of ortho-phosphoric acid to prevent in vitro conversion of MMF to MPA. Plasma concentrations of MPA were determined using a validated HPLC procedure. The median MPA AUC on day 6 (29.7 mg.h/L) after the first oral dose was slightly lower than the AUCs on the other study days (34.2, 33.8, and 33.8 mg.h/L on days 3, 5, and 10, respectively). Pairwise comparison of the individual days revealed statistically significant (P<0.05) differences between day 6 and day 3 and between day 5 and day 3. The Cmax on day 6 was significantly lower than that on study days 3 and 5. The bioavailability of MPA from the oral MMF formulation was estimated as the ratio of the AUC on day 6 or 10 to the AUC on day 5 when steady state was presumed to have been reached with the IV formulation. The mean ratios (expressed as percentage) for the log-transformed AUCs were 91.6% and 107.8% on days 6 and 10, respectively, relative to day 5. The 90% confidence interval (CI) on day 6 (79.3% to 105.8%) was marginally below the range (80%-125%) required to conclude that the formulations are bioequivalent, whereas on day 10 the 90% CI (93.3% to 124.7%) was within this range. In the case of the Cmax values, however, the 90% confidence intervals fell outside of this range (day 6, 57.2% to 92.8%; day 10, 70.6% to 114.9%). The results of this study show that heart transplant recipients receiving the IV formulation of MMF (1.5 g BID) are not subject to a greater drug exposure than that seen with the oral formulation (1.5 g BID) and that the oral MMF formulation shows excellent, high, and consistent bioavailability (mean 95%) based on comparison with the IV formulation.