[Studies on the pharmacokinetics and metabolism of tinofedrine]

Pharmacokinetics and biotransformation of l-(+)-alpha-(1-[(3,3-di-3-thienylallyl)-amino]-ethyl)-3-benzyl alcohol hydrochloride (tinofedrine hydrochloride, D 8955, Novocebrin) were investigated in rat and dog by means of the 3H-labelled drug. After i.v. administration similar biphasic time courses of the plasma levels are seen in the rat and the dog. The elimination is linear with a half-life of 3.0 and 3.8 h, respectively. After peroral administration 3H-tinofedrine is absorbed much more rapidly by the dog than by the rat. Radioactivity is subsequently eliminated from plasma by both species at nearly identical speed, which corresponds to that after i.v. administration. Quantitative analysis of the organ distribution after i.v. administration in the rat reveals a distinct affinity of 3H-tinofedrine for the lung. All tissue bindings, however, after both routes of administration are reversible. After preoral administration the drug is absorbed nearly quantitatively in the dog and in the rat with 50--63%. Only unchanged tinofedrine can be detected in the blood of the mesenteric veins. Tinofedrine is completely metabolized. In the rat and in the dog three different conjugates are formed, two of which are excreted with the bile. During their way through the intestine they are split again into tinofedrine, which is found in the feces. 3H-Tinofedrine after i.v. and peroral administration is mainly excreted fecally by the rat and the dog. This is caused by the great extent of the biliary excretion of the metabolites.