Plasma concentrations of timiperone and its reduced metabolite in the patients on timiperone

• Published in: Psychiatry and clinical neurosciences Vol. 52; no. 5; pp. 535 - 540
• Main Authors: SHIMODA, KAZUTAKA, SOMEYA, TOSHIYUKI, MORITA, SACHIYO, HIROKANE, GENTA, YOKONO, AYA, SHIBASAKI, MORIKAZU, TAKAHASHI, SABURO
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Oxford UK Blackwell Science Ltd 01.10.1998; Blackwell Publishing
• Subjects: Adolescent; Adult; Antipsychotic Agents - chemistry; Antipsychotic Agents - pharmacokinetics; Biological and medical sciences; Butyrophenones - chemistry; Butyrophenones - pharmacokinetics; Dose-Response Relationship, Drug; Female; haloperidol; Humans; ketone reductase; Male; Medical sciences; Middle Aged; Neuropharmacology; Oxidation-Reduction; Pharmacology. Drug treatments; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; reduced haloperidol; reduced timiperone; reduction; Schizophrenia - blood; Schizophrenia - drug therapy; Schizophrenia - enzymology; Structure-Activity Relationship; timiperone; Human; Metabolite; Neuroleptic; Psychotropic; Timiperone; Oral administration; Schizophrenia; Butyrophenone derivatives; Haloperidol; Psychosis; Chemotherapy; Treatment; Pharmacokinetics; Comparative study
• ISSN: 1323-1316; 1440-1819
• DOI: 10.1046/j.1440-1819.1998.00421.x

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).