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Plasma concentrations of timiperone and its reduced metabolite in the patients on timiperone
Author(s) -
SHIMODA KAZUTAKA,
SOMEYA TOSHIYUKI,
MORITA SACHIYO,
HIROKANE GENTA,
YOKONO AYA,
SHIBASAKI MORIKAZU,
TAKAHASHI SABURO
Publication year - 1998
Publication title -
psychiatry and clinical neurosciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.609
H-Index - 74
eISSN - 1440-1819
pISSN - 1323-1316
DOI - 10.1046/j.1440-1819.1998.00421.x
Subject(s) - chemistry , reductase , metabolite , endocrinology , body weight , haloperidol , medicine , enzyme , biochemistry , dopamine
Plasma levels of timiperone (TIM) and reduced timiperone (RTIM) were determined in 10 schizophrenic patients who were treated with TIM. Activities of ketone reductase in red blood cells (RBC) were assayed using TIM and haloperidol (HAL) as substrates. Plasma levels of TIM and RTIM ranged from 3.2 ng/mL to 9.5 ng/mL and from 1.7 ng/mL to 7.6 ng/mL, respectively, and ∼four‐fold inter‐individual variations in RTIM/TIM (0.37–1.43, 0.67 ± 0.25) were observed. There were significant and positive correlations between plasma levels of TIM or RTIM with the daily doses of TIM (mg/kg body weight); TIM (ng/mL) = 19.5 × daily dose of TIM (mg/kg) + 1.3, r = 0.79, n = 18, P < 0.01; RTIM (ng/mL) = 13.1 × 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 predicted, which is ∼60% that of HAL. The activity of TIM reductase in RBC was determined as ∼70% of HAL reductase in RBC, although the correlation between the activities of TIM reductase and HAL reductase in RBC was high (r = 0.98, n = 10, P < 0.001).