MacPhee G J, Goldie C, Roulston D, Potter L, Agnew E, Laidlaw J, Brodie M J
Eur J Clin Pharmacol. 1986;30(1):37-42. doi: 10.1007/BF00614193.
The effect of a single dose of carbamazepine (CBZ), 10 mg kg-1, on a battery of simple psychomotor tests was investigated in 12 healthy subjects (6 male, 6 female) in a balanced randomised double blind placebo controlled cross-over study. Psychomotor testing and blood sampling for total and free plasma CBZ, and CBZ 10, 11 epoxide concentration were performed at 10, 12, 14, 16, 18 and 34 h after oral dosing (23.00 h the previous evening). CBZ impaired i) critical flicker fusion threshold frequency at all time points up to 18 h (p less than 0.005); ii) total choice reaction time at 10 h (p less than 0.005) and 18 h (p less than 0.008); iii) card sorting at 14 h (p less than 0.001). No significant effect on finger tapping was noted. Subjects adjudged themselves more sedated on CBZ as compared to placebo at 12, 14 and 16 h (p less than 0.008). Plasma total and free CBZ concentrations (mean +/- SD) peaked at 10 h (8.8 +/- 0.2 mg 1-1) and 16 h (1.88 +/- 0.3 mg 1-1) after dosing respectively. CBZ 10, 11 epoxide values were all less than 10% of total CBZ concentrations and, therefore, were unlikely to contribute to the pharmacodynamic effect. Total choice reaction time was significantly more impaired in females (p less than 0.05) but no sex difference occurred with the other tests or CBZ concentrations at any time point. No significant correlations were found between individual total or free CBZ concentrations and corresponding test performances at each time point.(ABSTRACT TRUNCATED AT 250 WORDS)
在一项平衡随机双盲安慰剂对照交叉研究中,对12名健康受试者(6名男性,6名女性)研究了单剂量10 mg/kg卡马西平(CBZ)对一系列简单精神运动测试的影响。口服给药(前一晚23:00)后10、12、14、16、18和34小时进行精神运动测试以及采集血样,检测血浆总CBZ和游离CBZ以及CBZ 10,11 - 环氧化物浓度。CBZ损害了:i)至18小时所有时间点的临界闪烁融合阈值频率(p<0.005);ii)10小时(p<0.005)和18小时(p<0.008)的总选择反应时间;iii)14小时的卡片分类(p<0.001)。未观察到对手指敲击有显著影响。在12、14和16小时,与安慰剂相比,受试者判定自己服用CBZ后更困倦(p<0.008)。给药后血浆总CBZ和游离CBZ浓度(均值±标准差)分别在10小时(8.8±0.2 mg/L)和16小时(1.88±0.3 mg/L)达到峰值。CBZ 10,11 - 环氧化物值均低于总CBZ浓度的10%,因此不太可能对药效学效应有贡献。女性的总选择反应时间受损更显著(p<0.05),但在其他测试或任何时间点的CBZ浓度方面未出现性别差异。在每个时间点,个体总CBZ或游离CBZ浓度与相应测试表现之间未发现显著相关性。(摘要截断于250字)