Effect of alcohol coadministration on the plasma and brain concentrations of cocaine in rats.
We investigated the effect of intravenous alcohol coadministration on the pharmacokinetics of cocaine in awake, freely moving rats using the microdialysis technique. Alcohol coadministration resulted in faster rate of cocaine absorption after intraperitoneal administration leading to higher cocaine plasma concentration. The higher plasma cocaine concentration resulted in a proportional increase in the cocaine brain extracellular fluid concentration. However, cocaine brain extracellular fluid/plasma distribution ratio, determined from the ratio of the corresponding cocaine area under the concentration-time curves, was not affected by alcohol coadministration. Cocaethylene was detected only after administration of cocaine + alcohol. The brain extracellular fluid/plasma distribution ratio of cocaethylene was similar to that of cocaine. The higher cocaine concentrations in plasma and brain extracellular fluid, in addition to the formation of the pharmacologically active metabolite cocaethylene are, at least partially, responsible for the increased cocaine effects produced after administration of this drug combination.
Hedaya
M A
MA
Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman 99164-6510, USA.
Pan
W J
WJ
D000818:Animals; D001923:Brain Chemistry; D003042:Cocaine / Q000031:analogs & derivatives / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D004357:Drug Synergism; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005110:Extracellular Space / Q000737:chemistry; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000431:Ethanol; C066444:cocaethylene; D003042:Cocaine