Shimoda K, Someya T, Morita S, Hirokane G, Yokono A, Shibasaki M, Takahashi S
Department of Psychiatry, Shiga University of Medical Science, Otsu, Japan.
Psychiatry Clin Neurosci. 1998 Oct;52(5):535-40. 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 approximately 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 x daily 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 predicted, which is approximately 60% that of HAL. The activity of TIM reductase in RBC was determined as approximately 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).
对10名接受替米哌隆（TIM）治疗的精神分裂症患者测定了血浆中替米哌隆（TIM）和还原替米哌隆（RTIM）的水平。以TIM和氟哌啶醇（HAL）为底物，测定了红细胞（RBC）中酮还原酶的活性。TIM和RTIM的血浆水平分别为3.2 ng/mL至9.5 ng/mL和1.7 ng/mL至7.6 ng/mL，并且观察到RTIM/TIM存在约四倍的个体间差异（0.37 - 1.43，0.67±0.25）。TIM或RTIM的血浆水平与TIM的每日剂量（mg/kg体重）之间存在显著正相关；TIM（ng/mL）= 19.5×TIM的每日剂量（mg/kg）+ 1.3，r = 0.79，n = 18，P < 0.01；RTIM（ng/mL）= 13.1×TIM的每日剂量（mg/kg）+ 0.7，r = 0.73，n = 18，P < 0.001。给予0.3 mg/kg的TIM时，预测TIM的血浆水平为7.15 ng/mL，约为HAL的60%。尽管RBC中TIM还原酶和HAL还原酶的活性之间相关性很高（r = 0.98，n = 10，P < 0.001），但RBC中TIM还原酶的活性测定为RBC中HAL还原酶活性的约70%。
