No abstract

Pharmacokinetic interactions of ethanol with other drugs, including its effects upon drug metabolite disposition, are reviewed in terms of clearance concepts. This approach is particularly useful in understanding the mechanisms of ethanol-drug interactions, i.e. in separating the effects of ethanol upon drug clearance, volume of distribution and plasma protein binding. The application of clearance concepts provides the basis for understanding the qualitative differences in ethanol interactions with low and high hepatic extraction ratio drugs. The effects of short and long term ethanol consumption upon different types of drug metabolism (oxidative, acetylation and glucuronidation) have been considered. Long term ethanol consumption may increase the clearance of a drug by induction of oxidative metabolism whereas short term consumption may decrease the clearance of such a drug. Clearance by N-acetylation appears to be increased in the presence of ethanol, and clearance by conjugation to glucuronic acid is decreased for some drugs by single-dose consumption of ethanol.

The evidence is reviewed that violent and suicidal behavior is associated with a deficiency of the serotonin system and that individuals with poor impulse control tend to become hypoglycemic during an oral glucose tolerance test, and have low levels of 5-hydroxyindole acetic acid in the cerebrospinal fluid. It is postulated that serotonergic deficits may predispose individuals to poor impulse control, disturbance of glucose metabolism, alcohol abuse, violent behavior and suicide.

In a randomized cross-over trial on six healthy medical students, alcohol (Ig/kg) ingested as whisky did not modify significantly the absorption of 200 mg of doxycycline (DC) given in two tablets. Cheap red wine with a clear taste of acetic acid postponed the absorption of DC for 2-3 hours without affecting its 24-hour AUC or urinary excretion significantly. Another similar trial with other wines on 8 healthy students suggested that good regular wines do not retard D C absorption irrespective of their tannic acid content. However, acetic acid may postpone DC absorption by possibly slowing the rate of gastric emptying.