The disposition of a novel pyrimidoindole, ciclazindol, in the rat and patas monkey
Swaisland, A.J.; Pierce, D.M.; Franklin, R.A.
Drug Metabolism and Disposition the Biological Fate of Chemicals 5(5): 419-424
1977
ISSN/ISBN: 0090-9556 PMID: 20289 Document Number: 118817
The disposition of orally administered 2-14C ciclazindol, an antidepressant, was investigated in rats and red patas monkeys [Erythrocebus patas]. Absorption was more rapid in the rat than in the monkey. Although absorption was extensive in both species, peak plasma levels were considerably higher in the monkey. Plasma half-life of the drug was approximately 4 h in both species. Unchanged ciclazindol represented < 20% of total drug-related substances in the plasma, indicating rapid metabolism. Tissue distribution of radioactivity was investigated by tissue excision in both species and by whole-body autoradiography in male rats; in both species the distribution was typical of a basic, lipophilic drug. Ciclazindol was extensively bound to plasma proteins in both species; saturation of binding sites was seen at a lower concentration in monkey plasma than in rat plasma. Urinary recovery of administered radioactivity was 37% in male rats, 50% in female rats and 65% in monkeys. Renal excretion was multiphasic in both species; half-lives of the last 2 phases measured were approximately 7 and 20 h in rats and 6.5 and 30 h in the monkey. In rats, almost 10% of the 14C in the dose appeared as exhaled CO2.