ALCOHOL PRETREATMENT ALTERS THE METABOLIC PATTERN AND ACCELERATES COCAINE METABOLISM IN PIGS

We investigated whether alcohol pretreatment would affect the disposit ion and metabolic pattern of intravenously (i.v.) administered cocaine in pigs. Six pigs (Group A) received alcohol (1 g/kg/day) and six pig s (control; Group D) received an equal volume of isocaloric dextrose 4 4% in water for 10 days via an intragastric tube. On day 11, arterial samples were taken for five hours following an intravenous administrat ion of cocaine hydrochloride (4 mg/kg). Plasma concentrations of cocai ne and its major metabolites were analyzed by HPLC method. Significant decrease in plasma half-life (10 +/- 1.2 vs. 18.7 +/- 1.4 min), and s ignificant increases in apparent volume of distribution (73 +/- 6 vs. 51 +/- 31) and clearance (5.37 +/- 0.6 vs. 1.82 +/- 0.1 l/min) were se en in alcohol pretreated pigs as compared with control pigs (P < 0.05) , Significant increases in plasma concentrations of benzoylecgonine (P < 0.05), and insignificant differences in ecgonine methyl ester and n orcocaine levels were seen between the two groups. Neither ecgonine no r cocaethylene was detected in the blood samples. Our data show that a lcohol administration for ten days accelerated the elimination of i.v. administered cocaine and altered its metabolic pattern in pigs.