Pharmacokinetics of 14C-activity after the administration of 14C-azimexone in rats.

The pharmacokinetics of 14C-activity were studied in male Sprague-Dawley rats over 24 and 288 h periods after oral i.v. administration respectively. After oral administration rapid and complete absorption of azimexone occurred. The elimination of radioactivity from plasma after i.v. administration could be best described by an open four-compartment-system yielding a terminal half-life of 74.45 h indicating the existence of deep compartment for azimexone or its metabolites. The renal clearance of 14C-activity decreased considerably after i.v. administration with progressing time. This points to an extensive metabolism of azimexone. Fifty-seven and sixty-seven per cent of the given 14C-activity could be recovered in urine within 24 h after i.v. and p.o. administration respectively and in both cases less than 1% of the doses in feces. Studies on the distribution of the labelled substance 24 h after i.v. administration showed highest concentration in gastric contents, spleen thyroid gland and bone marrow. Twelve days after i.v. administration the ratio of the 14C-content in organ/plasma was greatly increased for spleen, thymus, lung, bone marrow and thyroid gland as compared with the conditions 24 h after administration. Thus it can be assumed that the target organs for the immunomodulating activity of the drug belong to the deep compartment of azimexone or its metabolites.