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 readin g to higher cocaine plasma concentration, The higher plasma cocaine co ncentration resulted in a proportional increase in the cocaine brain e xtracellular fluid concentration, However, cocaine brain extracellular fluid/plasma distribution ratio, determined from the ratio of the cor responding cocaine area under the concentration-time curves, was not a ffected by alcohol coadministration, Cocaethylene was detected only af ter administration of cocaine + alcohol, The brain extracellular fluid /plasma distribution ratio of cocaethylene was similar to that of coca ine, The higher cocaine concentrations in plasma and brain extracellul ar 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 c ombination.