EFFECTS OF ETHANOL ON INTESTINAL-ABSORPTION OF DRUGS .1. IN-SITU STUDIES WITH CIPROFLOXACIN ANALOGS IN NORMAL AND CHRONIC ALCOHOL-FED RATS

The effect of chronic alcohol intake on the intestinal absorption of s even compounds belonging to a homologous series (ciprofloxacin derivat ives) was evaluated using an in situ rat gut technique that measures t he intrinsic absorption rates of the compounds both in control and chr onic alcohol-fed rats. For chronic alcohol treatment, the animals were fed a liquid diet containing ethanol (36% of calories), whereas an is ocaloric diet was given to the pair-fed control animals. The biophysic al absorption model, relating the intestinal absorption rate constants and partition indexes of the tested compounds, was then established e ither for control or alcohol-fed animals, Differences were analyzed an d tentatively interpreted on the basis of general diffusion principles . Results revealed that, in chronic alcohol-fed animals, hydrophilic h omologs are absorbed at a significantly faster rate than in control on es, whereas lipophilic homologs do not change their absorption rate re lative to controls. Results demonstrate that the bulk polarity of the microvillous lipoidal membrane is enhanced by chronic ethanol intake, whereas basic features of the aqueous boundary layer are not altered. These observations suggest that the physicochemical properties of the compounds are an important factor in explaining the influence of chron ic alcohol intake on passive intestinal absorption of xenobiotics. The possible practical implications of our results are discussed from a s peculative viewpoint.