Metabolism of 14C-moxisylyte in hairless rat. Comparison between intravenous and oral route.

The pharmacokinetics of 14C-thymoxamine (4-(2-dimethylaminoethoxy)-5- isopropyl-2-methyl phenyl acetate hydrochloride) (moxisylyte, Carlytène) was studied on female hairless rats. Animals received 5 mg/kg of thymoxamine-HCl (CAS 964-52-3) intravenously or orally. 14C-thymoxamine was both rapidly and entirely absorbed after oral administration, Tmax value was observed at 0.25 h. The decrease of the total radioactivity followed a biexponential mode. After intravenous and oral administration, the apparent half-live of distribution were 0.20 and 0.31 h, respectively, whereas the apparent half-live of elimination were 9.6 (i.v.) and 8 h (p.o.). The nature and proportions of thymoxamine metabolites recovered in the plasma varied according to the route of administration. After intravenous administration, desacetyl-thymoxamine (DAT) + desacetyl-desmethyl-thymoxamine (DMAT), sulphate conjugates and glucuronides of DAT + DMAT represented 12, 21 and 63%, respectively. After oral administration, the values were 0, 21 and 79%, respectively. These results underlined the importance of the hepatic first-past effect which induced the disappearance of DAT and DMAT, and increased the levels of glucuronides when thymoxamine was orally administered. The level of sulphate conjugates for DAT and DMAT seems always constant.