Metabolism of Oxisuran, an Immunosuppressant, by the Rat

Abstract

1. The pharmacodynamics and biotransformation of oxisuran were studied in rats, a species in which the drug has immunosuppressive activity. Orally administered [¹⁴C]oxisuran was absorbed rapidly and produced max. blood radioactivity concentrations over the period from 0.5 to 3 h. Probably influenced by enterohepatic circulation, the ¹⁴C blood level declined gradually with a half-time of approx. 10 h. Renal excretion was the principal route of elimination for the drug and its metabolites.

2. The metabolism of oxisuran involved oxidation and reduction as phase 1 reactions. The minor pathway involved oxidation of oxisuran to its sulphone and reduction of this ketone sulphone to the corresponding alcohol sulphone. The major pathway involved reduction followed by oxidation to form the same end product.

3. The reduction of oxisuran to its alcohol created a second asymmetric centre and yielded two isomers which were resolved by g.l.c. The four metabolites were identified by t.l.c., elemental analyses and autoradiography in comparison with available synthetic preparations.

4. The reduced oxisuran isomers are considered to contribute to the immunosuppressive activity of the parent drug.