Concentration‐time profiles of ethanol and acetaldehyde in human volunteers treated with the alcohol‐sensitizing drug, calcium carbimide.

1. The disposition kinetics of ethanol and its toxic metabolite acetaldehyde were investigated in 10 healthy male volunteers who ingested 0.25 g kg‐1 ethanol after an overnight fast. This dose of ethanol was given 2 h after they swallowed a tablet of either calcium carbimide CC (50 mg), a potent inhibitor of low Km aldehyde dehydrogenase (ALDH), or placebo according to a single‐blind crossover design. 2. The pulmonary blood concentrations of ethanol and acetaldehyde were estimated indirectly by means of a gas chromatographic method modified for analysis of end‐expired breath. This non‐invasive sampling technique allowed replicate determinations at 15 min intervals. 3. The distribution volume of ethanol (V) was 0.64 +/‐ 0.023 1 kg‐1 after CC and 0.68 +/‐ 0.026 l kg‐1 after placebo treatment (P greater than 0.05). The zero order slope of the blood‐ ethanol decay profile (ko) decreased by about 5% when low Km ALDH was inhibited. The elimination of ethanol from the body (V X ko) was 1.9 +/‐ 0.051 mmol kg‐1 h‐1 after CC compared with 2.11 +/‐ 0.056 mmol kg‐1 h‐1 in placebo control experiments (P less than 0.001). The area under the ethanol concentration time curve (0–180 min) increased after CC treatment implying a change in clearance. 4. The disposition of acetaldehyde was markedly different in subjects pretreated with CC. The peak blood‐concentrations, estimated by analysis of breath, ranged from 40‐242 mumol l‐1 compared with 1.7‐6.5 mumol l‐1 after placebo.(ABSTRACT TRUNCATED AT 250 WORDS)