Impact of gastric emptying on the pharmacokinetics of ethanol as influenced by cisapride

Aims To examine the influence of cisapride on the pharmacokinetics of ethan ol and the impact of gastric emptying monitored by the paracetamol absorpti on test. Methods Ten healthy male volunteers took part in a cross-over design experi ment. They drank a moderate dose of ethanol 0.30 g kg(-1) body weight exact ly 1 h after eating breakfast either without any prior drug treatment or af ter taking cisapride (10 mg three times daily) for 4 consecutive days. In a separate study, the same dose of ethanol was ingested on an empty stomach (overnight fast). Paracetamol (1.5 g) was administered before consumption o f ethanol to monitor gastric emptying. Venous blood was obtained at 5-10 mi n intervals for determination of ethanol by headspace gas chromatography an d paracetamol was analysed in serum by high performance liquid chromatograp hy (h.p.l.c.). Results The maximum blood-ethanol concentration (C-max) increased from 3.8 +/- 1.7 to 5.6+/-2.3 mmol l(-1) (+/- s.d.) after treatment with cisapride ( 95% confidence interval CI on mean difference 0.28-3.28 mmol l(-1)). The ar ea under the blood-ethanol curve (AUC) increased from 6.3 +/- 3.5 to 7.9 +/ - 2.6 mmol l(-1) h after cisapride (95% CI -0.74-3.9 mmol l(-1) h). The mea n blood ethanol curves in the cisapride and no-drug sessions converged at a pproximate to 2 h after the start of drinking. Both C-max and AUC were high est when the ethanol was ingested on an empty stomach (C-max 9.5 +/- 1.7 mm ol l(-1) and AUC 14.6 +/- 1.9 mmol l(-1) h), compared with drinking 1 h aft er a meal and regardless of pretreatment with cisapride. Conclusions A small but statistically significant increase in C-max occurre d after treatment with cisapride owing to faster gastric emptying rate as s hown by the paracetamol absorption test. However, the rate of absorption of ethanol, as reflected in C-max and AUC, was greatest after drinking the al cohol on an empty stomach. The cisapride-ethanol interaction probably lacks any clinical or forensic significance.