Pharmacokinetic Studies on Clopenthixol Decanoate; A Comparison with Clopenthixol in Dogs and Rats

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Abstract
The release from the depot, hydrolysis and distribution in the organism, as well as the metabolism and elimination of i.m. injected clopenthixol decanoate in Viscoleo [psychotropic agent] were studied in dogs and rats with radioactive and non-labeled drug after single as well as repeated administration. The depot effect of clopenthixol decanoate given i.m. in oil compared to orally administered clopenthixol is demonstrated. The amounts of drug remaining at the site of injection in dogs suggest monoexponential release of drug from the depot and a half-life of 4-5 days. Rapid hydrolysis to clopenthixol in the organism was indicated by in vitro experiments and in vivo findings. Clopenthixol was the main compound in the organism after single and repeated doses. The clopenthixol formed by hydrolysis appeared to be metabolized in the same way as clopenthixol given orally, i.e., by dealkylation of the side chain and by S-oxide and N-oxide formation. The elimination pattern with predominant fecal excretion also appeared to be the same after clopenthixol and its esterified derivative, apart from the reflection in the latter case of the slow release from depot. A rapid exchange in the organism between 3H from the drugs and hydrogen from the body water was demonstrated. This has to be considered in studies with 3H labeled drugs, where estimation of total radioactivity gives the sum of 3H in drug, metabolites and water.