Effects of food, mild stress, and distributed intake on the absorption and plasma concentration-time profile of orally ingested ethanol in pigtailed macaques.

Abstract

To evaluate the possibility of estimating ethanol plasma level from a record of voluntary intake, the effects of food, mild stress, and distributed dosing on the fraction of ethanol absorbed and the relative exposure to circulating blood ethanol were determined in four adult male pigtailed macaques (Macaca nemestrina). The animals received 0.6 g/kg ethanol IV and orally after an 18-hour fast, after a small meal, and under mild stress; distributed dosing was evaluated for the oral route only. The concentration-time profile for the oral/fasting condition was very similar to that following an IV dose. The dose was completely absorbed and peak plasma level occurred about 30 min after ingestion. Peak plasma concentration was reduced by 42% following a small meal, 29% following mild stress, and 18% following distribution of the dose over 60 min. The time to peak concentration was more than doubled by distributed dosing. Relative exposure was reduced by 18 to 27% by all conditions of oral administration except feeding, which caused a 52% reduction. The fraction of ethanol absorbed was influenced only by feeding, which caused a reduction of 20%. The magnitude of changes in concentration-time profile produced by such factors precludes accurate estimation of blood levels from records of voluntary intake. Furthermore, the effects of social factors on voluntary ethanol consumption may be mediated by centrally controlled changes in gastrointestinal function that alter the rate and extent of absorption of the drug.