Serum levels of the isomers of clopenthixol in patients given cis(Z)-clopenthixol or cis(Z)/trans(E)-clopenthixol

Abstract

The serum levels of the two geometric isomers of clopenthixol and N-dealkylated clopenthixol were estimated in 9 patients, who received cis(Z)-clopenthixol (Cisordinol, Clopixol tabl.) in one period and the double dose of cis(Z)/trans(E)-clopenthixol (Sordinol, Ciatyl) in another period. Nearly equal concentrations of the neuroleptically active isomer, cis(Z)-clopenthixol, were found in the two periods. This finding is in agreement with the clinical experience, but in disagreement with the administered amounts of cis(Z)-clopenthixol, which were larger when the cis(Z)-isomer was given alone. Highly significant correlations were found between dose and mean serum level of cis(Z)-clopenthixol and between dose and area under the serum concentration curves for 8 of the patients, the ninth patient, who had received additional medication showed deviating results. No indication of transformation of cis(Z)-clopenthixol into trans(E)-clopenthixol or vice versa was found. Trans(E)-clopenthixol was found in the serum samples even after administration for one week with the cis(Z)-clopenthixol tablets indicating a relatively long half-life of the trans(E)-isomer. The cis(Z)-isomer of N-dealkyl clopenthixol was found in about the same concentration as cis(Z)-clopenthixol in both periods, while trans(E)-N-dealkyl clopenthixol occurred in about 4 times higher concentrations in patients who had either been given cis(Z)/trans(E)-clopenthixol before they went into the study or had received it in the first period of this study.