PLASMA-CONCENTRATIONS OF TIMIPERONE AND ITS REDUCED METABOLITE IN THEPATIENTS ON TIMIPERONE

Plasma levels of timiperone (TIM) and reduced timiperone (RTIM) were d etermined in 10 schizophrenic patients who were treated with TIM. Acti vities of ketone reductase in red blood cells (RBC) were assayed using TIM and haloperidol (HAL) as substrates. Plasma levels of TIM and RTI M ranged from 3.2 ng/mL to 9.5 ng/mL and from 1.7 ng/mL to 7.6 ng/mL, respectively, and similar to four-fold inter-individual variations in RTIM/TIM (0.37-1.43, 0.67 +/- 0.25) were observed. There were signific ant and positive correlations between plasma levels of TIM or RTIM wit h the daily doses of TIM (mg/kg body weight); TIM (ng/mL) = 19.5 x dai ly dose of TIM (mg/kg) + 1.3, r = 0.79, n = 18, P < 0.01; RTIM (ng/mL) = 13.1 x daily dose of TIM (mg/kg) + 0.7, r = 0.73, n = 18, P < 0.001 ). Given 0.3 mg/kg of TIM, a plasma level of TIM as 7.15 ng/mL was pre dicted, which is similar to 60% that of HAL. The activity of TIM reduc tase in RBC was determined as similar to 70% of HAL reductase in RBC, although the correlation between the activities of TIM reductase and H AL reductase in RBC was high (r = 0.98, n = 10, P < 0.001).