Alcohol pretreatment alters the metabolic pattern and accelerates cocaine metabolism in pigs.
We investigated whether alcohol pretreatment would affect the disposition and metabolic pattern of intravenously (i.v.) administered cocaine in pigs. Six pigs (Group A) received alcohol (1 g/kg/day) and six pigs (control; Group D) received an equal volume of isocaloric dextrose 44% in water for 10 days via an intragastric tube. On day 11, arterial samples were taken for five hours following an intravenous administration of cocaine hydrochloride (4 mg/kg). Plasma concentrations of cocaine 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 significant 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 seen 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 norcocaine levels were seen between the two groups. Neither ecgonine nor cocaethylene was detected in the blood samples. Our data show that alcohol administration for ten days accelerated the elimination of i.v. administered cocaine and altered its metabolic pattern in pigs.
Kambam
J R
JR
Department of Anesthesiology, Vanderbilt University Hospital, Nashville, TN 37232.
Franks
J J
JJ
Janicki
P K
PK
Mets
B
B
vd Watt
M
M
Hickman
R
R
D000818:Animals; D001711:Biotransformation; D003042:Cocaine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000431:Ethanol / Q000493:pharmacokinetics / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D013552:Swine
D000431:Ethanol; D003042:Cocaine