Absorption, distribution, metabolism and excretion of cizolirtine, a new analgesic compound, in rat and dog

1. The pharmacokinetics of cizolirtine citrate, a new analgesic compound, were studied in the rat and dog following single oral and intravenous doses. 2. Absorption of radioactivity was fast and complete regardless of the species, and no dose and food-related differences were found. However, the elimination half-life of unchanged cizolirtine was shorter in rat than in dog. 3. Tissue distribution of total radioactivity in rat differed widely and a high affinity for liver, kidney, gastrointestinal and pigmented tissues was observed. In blood and almost all tissues the highest concentrations were reached at 20 min; beyond that time the decline of radioactivity in most tissues was parallel to that in blood. 4. The percentage of radioactivity excreted in the rat was 68 % in urine and 21 % in faeces, the latter being apparently due to drug enterohepatic circulation. In the dog, 92 and 4 % of the radioactivity was found in urine and faeces respectively. The contribution of renal excretion to cizolirtine elimination was < 5 % in rat and 20 % in dog. Twelve metabolites were detected in rat and six in the dog by radio-hplc analysis of urine.