Pharmacokinetic study of maleate acid of 2-(N,N-dimethylaminoethanol-14C1)-cyclohexylpropionate (cyprodenate) and of N,N-dimethylaminoethanol-14C1 in animals.

The localization, distribution, and elimination of maleate acid 2-(N,N-dimethylaminoethanol-14C1)-cyclohexylpropionate (14C-cyprodenate, Actebral) was studied in rats and pigs. Beside this, dimethylaminoethanol-14C (DMAE) was also administered to rats enabling a comparison of the pharmacokinetics of the two 14C-labelled molecules to be made. The study of the localization by autoradiography and the study of the quantitative distribution of the radioactivity showed that cyprodenate, a psychotonic drug, diffused more rapidly than DMAE through the hemo-encephalic barrier. However, it was also observed that the radioactivity found in the brain rises continually as a function of time, regardless of the product administered. The two labelled products were primarily excreted in the urine (30-35 per cent of the dose in 72 h in rats and 6 per cent of the dose in 48 h in pigs) following oral administration of cyprodenate. Radioactivity found in the feces was practically nil and in rats the biliary elimination of the drug was very weak. Thus, whichever animal is used, it was found that 14C-cyprodenate is totally absorbed. Radioactivity expired as 14CO2 was negligible (around 1 per cent of the administered dose in 8 h), however, this value increases as a function of time, becoming 4 per cent in 24 h. In rats the maximum radioactivity in the blood was found at 45 min to 1 h after oral administration of 14C-cyprodenate. These values decrease slowly until 3 h when they begin to increase again. The rising of the blood level values is practically the same for pigs, the maximum being attained at 1 h. Therefore, whatever route of administration, whichever dose or animal, we always found a progressive elevation of the protein binding to the plasma proteins for these two labelled products in vivo.