The metabolic fate of 14C or 35S labelled tiadenol in rabbit after i.v. and oral administration.

Tiadenol is a hypocholesterolemic drug that inhibits the early steps of cholesterol synthesis. No pharmacokinetic data have thus far been reported for man and few for animals. We investigated the pharmacokinetics, biotransformation and distribution of two differently labelled tiadenol molecules (14C and 35S) in the rabbit. Following a short protocol (up to 8 h), a regular decrease of the plasma radioactivity was observed after i.v. route for 4 or 5 h and plateaued thereafter. Most of the radioactivity was found in the urine, the lungs and the liver with low levels in bile and feces. By oral route, the plasma radioactivity increased regularly and decayed for a short period. Thereafter, a second increase was observed. Drug and metabolites accumulated in the kidneys and in the liver but most of the radioactive compounds were recovered from the urine. From results obtained with a longer protocol (4 days in a metabolic cage), it could be extrapolated that 10 to 15 days are necessary to completely clear the drug. Tiadenol was extensively metabolized with a wide tissue distribution. The main metabolites identified were oxidation products (free or conjugated). No statistically significant differences in biotransformation were found between the two differently labelled tiadenol molecules.