Alcohol effects during acamprosate treatment: a dose-response study in humans.
BACKGROUND
Acamprosate (calcium acetyl homotaurinate) reduces alcohol intake in animals and increases abstinence rates in alcohol-dependent persons. Acamprosate's mechanism of action, however, remains poorly understood. In order to examine whether acamprosate/alcohol interactions contribute to acamprosate's efficacy, the present double-blind, placebo-controlled human laboratory study examined effects of acamprosate on the pharmacokinetics and subjective, psychomotor, and physiological effects of alcohol in heavy drinkers.


METHODS
In a six-week within-subject design, participants were maintained on acamprosate (0, 2, and 4 g, p.o., double-blind, in counterbalanced order) for 11 days at each dose. Physiological, subjective, and psychomotor measures were collected daily during each dosing cycle. During each acamprosate dose condition, subjects were challenged with 0, 0.5, and 1.0 g/kg ethanol (p.o., counterbalanced order) during three separate laboratory sessions. Subjective, physiological, and psychomotor effects of alcohol, and breath alcohol levels were collected at baseline and at 30-min intervals for a 3-hr post-administration period.


RESULTS
Acamprosate alone did not substantially affect subjective, physiological, or psychomotor performance measures. Acamprosate did not alter alcohol pharmacokinetics, or alcohol-induced behavioral impairment or tachycardia, and most subjective alcohol effects were also unaltered by acamprosate as well. Although a trend appeared for acamprosate to increase subjective ratings of intoxication following the lower (0.5 g/kg) alcohol dose, adjustment for individual differences in blood alcohol level eliminated this effect, suggesting the trend was not due to a central effect of acamprosate.


CONCLUSIONS
Acamprosate does not alter alcohol pharmacokinetics, acute physiological or psychomotor alcohol effects, or most subjective alcohol effects.
Brasser
Susan M
SM
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224-6823, USA.
McCaul
Mary E
ME
Houtsmuller
Elisabeth J
EJ
D000077443:Acamprosate; D000328:Adult; D000428:Alcohol Drinking / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D000435:Alcoholic Intoxication / Q000097:blood / Q000188:drug therapy / Q000523:psychology; D000704:Analysis of Variance; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D013654:Taurine / Q000008:administration & dosage* / Q000031:analogs & derivatives*
D013654:Taurine; D000431:Ethanol; D000077443:Acamprosate