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)