Abstract
Mycophenolate mofetil (MPM), a new immunosuppressant, is the morpholinoethyl ester of mycophenolic acid (MPA). The distribution in blood and pharmacokinetics of MPA after administration of MPM were examined. The plasma to erythrocyte concentration ratio was low (0.10-0.15). MPA existed in rat plasma as the highly bound form (bound fraction was 97.9 ± 0.57%). MPA disappeared from the systemic circulation with biexponential decay. After iv administration of MPM at the doses of 8.3, 16.7, and 33.3 mg/kg, the total clearance of MPA was 0.241 ± 0.056, 0.321 ± 0.126, and 0.317 ± 0.092 L/h/kg, respectively. The terminal elimination half-live were 5.17 ± 1.44, 8.89 ± 2.76, and 7.94 ± 2.94 h, respectively. After id administration of MPM at the doses of 8.3, 16.7, 33.3, and 50.0 mg/kg, the terminal elimination half-live were 6.41 ± 4.16, 4.49 ± 2.20, 7.58 ± 3.72, and 8.18 ± 1.32 h, respectively. The mean peak times were within 30min. The systemic availability of MPA after id administration of MPM (at 8.3, 16.7, and 33.3 mg/kg) was calculated using the corresponding mean AUCiv, and the values were 84.3 ± 35.0%, 69.9 ± 25.7%, and 63.6 ± 8.8%, respectively.
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