Repeated dosing with donepezil does not affect the safety, tolerability or pharmacokinetics of single-dose thioridazine in young volunteers.
Repeated dosing with donepezil does not affect the safety, tolerability or pharmacokinetics of single-dose thioridazine in young volunteers.
复制标题
在年轻志愿者中重复服用多奈哌齐不会影响单剂量硫利达嗪的安全性、耐受性或药代动力学。
DOI：
10.1111/j.1365-2125.2004.01800.x
复制
发表时间：
2004
影响因子：
3.4
通讯作者：
A. Johnston
中科院分区：
文献类型：
--
作者：
M. Ravic;S. Warrington;M. Boyce;K. Dunn;A. Johnston
目的
在健康受试者中研究稳态下多奈哌齐对单剂量硫利达嗪的安全性、耐受性和药代动力学的影响。
方法
一项在12名年龄在19-41岁之间的受试者（6名男性和6名女性）中进行的开放、双向、平衡交叉研究。在两个治疗阶段，受试者接受50 mg硫利达嗪单次口服给药;在一个阶段，硫利达嗪单独给药，在另一个阶段，硫利达嗪与最后一个15天口服剂量的多奈哌齐5 mg一起给药。当首次给予硫利达嗪时，“洗脱”期为1周，当最后给予硫利达嗪时，洗脱期为2周。每次给药后测量硫利达嗪的血浆浓度，并测定药代动力学参数。通过使用等效性分析测试相互作用，其中硫利达嗪为“参考”，硫利达嗪+多奈哌齐为“测试”方案。监测安全性和耐受性。
结果
根据AUC（0-tn）、AUC（0-无穷大）、t（（1/2））和t（max）的等效性分析判断，多奈哌齐对硫利达嗪的药代动力学无显著影响。“试验”和“参比”方案的C（max）非常相似，但置信区间太宽，无法确认等效性。多奈哌齐耐受性良好，而硫利达嗪与头晕目眩、疲劳和体位性低血压相关，无论是否同时给予多奈哌齐。
结论
多奈哌齐重复给药，每日5 mg，持续2周，对硫利达嗪的安全性、耐受性或药代动力学无显著影响。硫利达嗪耐受性差。
AIM
To investigate the effects of donepezil at steady state on the safety, tolerability and pharmacokinetics of a single dose of thioridazine, in healthy subjects.
METHODS
An open, two-way, balanced crossover study, in 12 subjects (six men and six women) aged 19-41 years. During both treatment periods, subjects received a single oral dose of 50 mg thioridazine; in one period the thioridazine was given alone, and in the other period it was given together with the last of 15 daily, oral doses of donepezil 5 mg. The 'washout' periods were 1 week when thioridazine was given first, and 2 weeks when thioridazine was given last. Plasma concentrations of thioridazine were measured after each dose, and pharmacokinetic parameters were determined. Interactions were tested by using an equivalence analysis in which thioridazine was the 'Reference' and thioridazine + donepezil the 'Test' regimen. Safety and tolerability were monitored.
RESULTS
Donepezil had no marked effect on the pharmacokinetics of thioridazine, as judged by the equivalence analysis of AUC(0-tn), AUC(0-infinity), t((1/2)) and t(max). C(max) was very similar in the 'Test' and 'Reference' regimens, but the confidence intervals were too wide to confirm equivalence. Donepezil was well tolerated, whereas thioridazine was associated with light-headedness, tiredness and postural hypotension, irrespective of whether or not donepezil was given concurrently.
CONCLUSIONS
Repeated dosing with donepezil, 5 mg daily for 2 weeks, had no significant effect on the safety, tolerability or pharmacokinetics of thioridazine. Thioridazine was poorly tolerated.
影响因子：
9.9
作者：
Rogers, SL;Farlow, MR;Walshe, TM
通讯作者：
Walshe, TM