Effect of food on the absorption of eptastigmine.
OBJECTIVE
The aim of the study was to evaluate the effects of food on the rate and extent of eptastigmine absorption in healthy volunteers.


METHODS
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.


RESULTS
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.


CONCLUSIONS
The ingestion of food significantly reduces the bioavailability of eptastigmine estimated by the assay of red blood cell acetylcholinesterase activity.
Bjornsson
T D
TD
Clinical Pharmacology Unit, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Troetel
W M
WM
Imbimbo
B P
BP
D000110:Acetylcholinesterase / Q000097:blood / Q000187:drug effects; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002091:Butyrylcholinesterase / Q000097:blood / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004244:Dizziness / Q000139:chemically induced; D004311:Double-Blind Method; D005502:Food; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D010830:Physostigmine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D016896:Treatment Outcome
D002800:Cholinesterase Inhibitors; C052450:physostigmine heptyl; D010830:Physostigmine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase