Crevoisier C, Handschin J, Barré J, Roumenov D, Kleinbloesem C
Department of Clinical Pharmacology, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Eur J Clin Pharmacol. 1997;53(2):135-9. doi: 10.1007/s002280050351.
To assess the effect of food on the pharmacokinetics of the antimalarial mefloquine and its major plasma metabolite in healthy volunteers.
In an open, two-way cross-over study, 20 healthy male volunteers who had fasted overnight were randomised to receive a single oral dose of 750 mg mefloquine in the absence or presence of a standardised, high-fat breakfast, administered 30 min before drug administration. Blood samples were taken at specific times over an 8-week period. Plasma concentrations of mefloquine and its carboxylic acid metabolite were determined by high-performance liquid chromatography for pharmacokinetic evaluation.
The parameters Cmax and AUC of both mefloquine and its metabolite were significantly (P < 0.05) higher under post-prandial conditions than under fasting conditions (mefloquine: mean Cmax 1500 vs 868 micrograms.l-1, mean AUC 645 vs 461 mg l-1.h; metabolite: Cmax 1662 vs 1231 micrograms.l-1, AUC 1740 vs 1310 mg l-1.h). The intersubject variability in Cmax and AUC of mefloquine was less than 30% (coefficient of variation). The time to peak plasma concentration of mefloquine was significantly shorter after food intake (17 vs 36 h). Compared with absorption in volunteers who had fasted, food did not alter t1/2 (mefloquine and its metabolite) and tmax (metabolite).
Under the conditions of this study, food increases the rate and the extent of mefloquine absorption. It is reasonable to recommend that mefloquine be administered with food in travellers receiving chemoprophylaxis and in patients on recovery receiving curative treatment. In acutely ill patients, mefloquine should be taken as soon as possible and administration with or shortly after meals should be attempted as soon as feasible.
评估食物对健康志愿者体内抗疟药甲氟喹及其主要血浆代谢产物药代动力学的影响。
在一项开放的双向交叉研究中，20名过夜禁食的健康男性志愿者被随机分为两组，分别在服用750毫克甲氟喹单剂量前30分钟，在无标准化高脂早餐或有标准化高脂早餐的情况下给药。在8周内特定时间采集血样。采用高效液相色谱法测定血浆中甲氟喹及其羧酸代谢产物的浓度，进行药代动力学评估。
餐后条件下，甲氟喹及其代谢产物的Cmax和AUC参数均显著高于空腹条件（甲氟喹：平均Cmax分别为1500和868微克·升-1，平均AUC分别为645和461毫克·升-1·小时；代谢产物：Cmax分别为1662和1231微克·升-1，AUC分别为1740和1310毫克·升-1·小时，P<0.05）。甲氟喹Cmax和AUC的个体间变异性小于30%（变异系数）。进食后甲氟喹达到血浆峰浓度的时间显著缩短（17小时对3·6小时）。与空腹志愿者的吸收情况相比，食物未改变甲氟喹及其代谢产物的t1/2和代谢产物的tmax。
在本研究条件下，食物可增加甲氟喹的吸收速率和吸收程度。对于接受化学预防的旅行者和接受康复治疗的患者，建议甲氟喹与食物同服。对于急性病患者，应尽快服用甲氟喹，并在可行时尽快尝试与餐同服或餐后不久服用。
