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

Abstract

The release from the depot, hydrolysis and distribution in the organsim as well as the metabolism and elimination of intramuscularly injected clopenthixol decanoate in Viscoleo have been studied in dogs and rats with radioactive as well as non-labelled drug after single as well as repeated administration. The studies clearly demonstrate the depot effect of clopenthixol decanoate given intramuscularly in oil compared to orally administered clopenthixol. 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 found to be the main compound in the organism after single as well as 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 tritium from the drugs and hydrogen from the body water was demonstrated. This has to be considered in studies with tritium labelled drugs, where estimation of total radioactivity gives the sum of tritium in drug, metabolites and water.