Hedaya M A, Pan W J
Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman 99164-6510, USA.
Drug Metab Dispos. 1997 May;25(5):647-50.
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.
我们使用微透析技术研究了静脉注射酒精与可卡因同时给药对清醒、自由活动大鼠体内可卡因药代动力学的影响。酒精与可卡因同时给药导致腹腔注射后可卡因的吸收速度加快，从而使可卡因血浆浓度升高。较高的血浆可卡因浓度导致可卡因脑细胞外液浓度成比例增加。然而，根据浓度-时间曲线下相应可卡因面积的比值确定的可卡因脑细胞外液/血浆分布比率不受酒精与可卡因同时给药的影响。仅在给予可卡因+酒精后才检测到可口乙酮。可口乙酮的脑细胞外液/血浆分布比率与可卡因相似。血浆和脑细胞外液中较高的可卡因浓度，以及具有药理活性的代谢物可口乙酮的形成，至少部分地导致了给予这种药物组合后可卡因作用增强。
