Single-Dose Pharmacokinetics of the New Immunosuppressant RS-61443 in the Rabbit

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Abstract
The pharmacokinetics of mycophenolic acid (MPA) were investigated in six New Zealand white rabbits following (i.v.) and (s.c.) administration of RS-61443. Plasma concentrations of MPA were analyzed by high-performance liquid chromatography (HPLC). Model-dependent and -independent parameters were calculated. Mycophenolic acid is rapidly cleared with a terminal half-life of approximately 1.0 h. The volume of distribution subsequent to i.v. administration indicates minimal distribution into tissues. The mean residence time and volume of distribution were greater for the s.c. as compared to the i.v. route of administration. The insignificant difference in the area under the curve between the two dosage routes infers that the bioavailability of RS-61443-derived MPA by the former route of administration is comparable to the latter. Trough concentrations at the doses administered are below the detection limit of the HPLC procedure. The implications of these findings in relation to the therapeutic monitoring of the drug are discussed.

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