[ On the metabolism of ethyl-DL-trans-2-dimethylamino-1-phenyl-cyclohex-3-ene-trans-1-carboxylate-hydrochloride (Tilidine-HCl). 2nd Communication: Studies with 14C-labelled substance on rats and dogs].

Absorption, distribution, metabolism and excretion of the potent analgesic ethyl-DL-trans-2-timethylamino-1-phenyl-chclohex-3-ene-trans-1-carboxylate-hydrochloride (tilidine-HCl, Gö 1261 C, active ingredient of Vloron) were investigated in rats and dogs, using the radioactively labelled substance. Following oral administration, tilidine-HCl is rapidly and completely absorbed from the duodenum. During absorption, tilidine undergoes a marked first-pass effect. In plasma several metabolites are found, part of them occurring in higher concentrations than the unchanged substance. The metabolites are also formed rapidly after parenteral administration, unchanged tilidine being found in higher concentrations than any of the metabolites at all times measured. Following both routes of administration, the Met. I (nortilidine), also possessing a strong analgesic activity, reaches similar plasma levels. 14C distribution studies in rats showed a relatively high concentration of the radioactivity in the excretory organs, liver and kidneys. In brain, muscle tissue and blood much lower 14C concentrations are found. The concentrations measured in the foetal organs correspond to those in the muscle tissue of the mother animals and are, therefore, much lower than in most maternal organs. The radioactivity is eliminated from the foetal organs at the same rate as from the maternal organs. Tilidine is rapidly and completely eliminated with the excrements, nearly exclusively in the form of metabolic products. Rats eliminate 50% of the given radioactivity via the kidneys. The relatively high fecal elimination is based on the biliary metabolites. Following intraduodenal and intravenous administration to rats with an interrupted enterohepatic circulation, about 80% of the dose is eliminated with bile. The biliary metabolites are partly reabsorbed. In dogs, approx. 80% of the applied radioactivity is eliminated with urine.