Bjornsson T D, Troetel W M, Imbimbo B P
Clinical Pharmacology Unit, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Eur J Clin Pharmacol. 1998 May;54(3):243-7. doi: 10.1007/s002280050453.
The aim of the study was to evaluate the effects of food on the rate and extent of eptastigmine absorption in healthy volunteers.
The study was carried out according to a double-blind, randomized, placebo-controlled, three-way cross-over design. On three separate occasions, six young subjects received 30 mg eptastigmine after a 12-h overnight fast (reference treatment), 30 mg eptastigmine 15 min after a standard breakfast (test treatment) and placebo 15 min after a standard breakfast (control treatment). Acetylcholinesterase activity in red blood cells was assayed 24 h after drug administration as a biological marker of eptastigmine plasma concentrations.
Mean maximum acetylcholinesterase inhibition (Imax) was 39.9% after eptastigmine without food and 33.1% after eptastigmine with food. Maximum inhibitions occurred at 4.75 h and 4.88 h after eptastigmine without and with food, respectively. Areas under the curve of acetylcholinesterase per cent inhibition from 0 to 8 h after drug administration (AUC0-8) were 198% h after eptastigmine without food and 124% h after eptastigmine with food. Ninety per cent confidence intervals of test/reference ratios for AUC0-8 and Imax exceeded the 0.80 to 1.20 limits, thus indicating that the two eptastigmine treatments cannot be considered bioequivalent. Mild and transient adverse events were recorded in three subjects receiving eptastigmine without food, one subject receiving eptastigmine with food and one subject receiving placebo.
The ingestion of food significantly reduces the bioavailability of eptastigmine estimated by the assay of red blood cell acetylcholinesterase activity.
本研究旨在评估食物对健康志愿者中依替膦明吸收速率和程度的影响。
本研究按照双盲、随机、安慰剂对照、三交叉设计进行。在三个不同的时间点，六名年轻受试者在禁食12小时后接受30毫克依替膦明（参比治疗），在标准早餐后15分钟接受30毫克依替膦明（试验治疗），以及在标准早餐后15分钟接受安慰剂（对照治疗）。给药24小时后测定红细胞中的乙酰胆碱酯酶活性，作为依替膦明血浆浓度的生物学标志物。
依替膦明空腹服用后乙酰胆碱酯酶平均最大抑制率（Imax）为39.9%，与食物同服后为33.1%。依替膦明空腹和与食物同服后的最大抑制率分别在4.75小时和4.88小时出现。给药后0至8小时乙酰胆碱酯酶抑制百分比的曲线下面积（AUC0-8），依替膦明空腹服用后为198%·小时，与食物同服后为124%·小时。AUC0-8和Imax的试验/参比比值的90%置信区间超出了0.80至1.20的范围，因此表明两种依替膦明治疗不能被认为具有生物等效性。在三名空腹接受依替膦明治疗的受试者、一名与食物同服依替膦明的受试者和一名接受安慰剂的受试者中记录到了轻微和短暂的不良事件。
摄入食物显著降低了通过红细胞乙酰胆碱酯酶活性测定评估的依替膦明的生物利用度。
