Pharmacokinetics and Metabolism of 14C-labelled Alinidine in Man and Dogs

Radioactively labelled alinidine was administered intravenously (10 mg) and orally (40 mg) to 5 healthy volunteers and beagle dogs (3 animals for each administration route: 0.1 mg/kg body weight i.v. and 1 mg/kg body weight p.o.). Alinidine was totally absorbed in both species. Regardless of the route of administration man excreted the drug via the kidneys within 12 hours, almost entirely in the unchanged form. The blood plasma curves in man followed a multiexponential decline (t 1/2 alpha : 35 sec, t 1/2 beta : 44 min, t 1/2 gamma : 210 min). The maximum plasma levels of the drug were recorded in man, 45 min after oral administration. However, the rather slow decline of plasma radioactivity observed in dogs, corresponded well with the delayed urinary excretion of alinidine (50% of the administered dose) in this species. Dogs metabolized the drug extensively; seven different metabolites including the parent compound were isolated from canine urine. considerable interindividual differneces were found concerning the quantitive but not the qualitative metabolic pattern of alinidine in dogs. Structural analysis by mass spectrometry revealed oxidation, hydroxylation, and cleavage products of alinidine, altered in its imidazolin and/or allylic moiety. In both species no traces of clonidine were found, which was a predicted metabolite formed by the removal of the allylic sidechain of alinidine.