Interaction of diazepam or lorazepam with alcohol

Abstract

Nine healthy volunteers in a double-blind, cross-over trial received diazepam (DZ) 10 mg, lorazepam (LZ) 2.5 mg, or placebo (P). Serum benzodiazepine (BZ) was bioassayed (radioreceptor method) and psychomotor tests were carried out on Day 1 (before and 1 h after the first dose) and on Day 4 (before and after the fifth dose). In each session alcohol 1 g/kg was administered 1.5 h after drug intake and the measurements were repeated twice. Serum BZ concentrations, expressed as DZ equivalents (µg/l), ranged from 390 to 440 and from 990 to 1240 measured 2 h 45 min after the first doses of DZ and LZ, respectively. On Day 1 BZ alone impaired psychomotor skills. LZ affected performance more in objective tests, but DZ was subjectively rated as causing more drowsiness. After the intake of alcohol, all groups showed impairment in various tests. The rank order was LZ+alcohol>DZ+alcohol>P+alcohol. Residual BZ activity on Day 4, measured 18 h after the fourth dose, averaged 290 and 450 µg/l after DZ and LZ, respectively. At the same time slight residual exophoria was found after both BZs. Tolerance to BZs on Day 4 was unambiguous only when drug effects were related to the bioassayed serum levels. The combined action of BZs and alcohol was similar on Days 1 and 4. However, a tendency to an increased drug-alcohol interaction during advanced treatment with DZ was seen in the body sway test. An attempt to clarify the very different serum BZ level after DZ and LZ was made in vitro by evaluating the displacement curves for DZ and LZ standards. The potencies of these BZs differed more in the presence than in the absence of serum. Thus, the psychomotor effects of DZ and LZ, as well as their BZ receptor occupation activity in serum, were not equipotent at doses 10 mg DZ and 2.5 mg LZ. The BZ-alcohol interaction was consistent at least over the first 5 doses.