Cocaethylene Formation Following Ethanol and Cocaine Administration by Different Routes
Cocaethylene Formation Following Ethanol and Cocaine Administration by Different Routes
复制标题
DOI：
10.1037/a0022950
复制
发表时间：
2011-04-01
影响因子：
2.3
通讯作者：
Jones, Reese T.
中科院分区：
文献类型：
--
作者：
Herbst, Ellen D.;Harris, Debra S.;Jones, Reese T.
乙醇改变可卡因的肝脏生物转化，导致酯交换成一种新的活性代谢物，可卡因。由于首次通过代谢，口服给药可能比静脉注射或烟熏给药产生相对较高的可卡因浓度。因此，我们比较了可卡因给药途径对可卡因形成和消除的影响。6名有经验的可卡因使用者分6次接受测试，间隔约1周。在所有条件下给予氘标记可卡因（d(5)）。在口服乙醇1.0g/kg或安慰剂后，分别口服可卡因-d(5) 2.0 mg/kg、静脉注射可卡因-d(5) 1.0 mg/kg和烟熏可卡因-d(5) 200 mg。在所有条件下，静脉注射小剂量的氘化coca乙烯（d(3)）来测定coca乙烯的形成。记录生理和主观效应，并用气相色谱-质谱法测定血浆可卡因-d(5)、可卡因-d(5)、可卡因-d(3)和苯甲酰ecgonine-d(5)。约24%（+/- 11%）的静脉注射可卡因转化为可卡因。口服途径（34% +/- 20）显著高于烟熏途径（18% +/- 11），且与静脉注射途径相比，可卡因的形成有显著性的趋势。在每条路线中，可卡因-乙醇组合比单独使用可卡因产生更大的心率和心率压产物的增加。当同时给予可卡因和乙醇时，吸烟或静脉注射后的整体中毒效应明显更大。通过不同途径服用可卡因会改变通过肝脏首过效应形成的可卡因的数量。增加的心血管和主观影响可能解释了联合用药的毒性和流行。
Ethanol alters the hepatic biotransformation of cocaine, resulting in transesterification to a novel active metabolite, cocaethylene. Because of first pass metabolism, oral drug administration might be expected to produce relatively larger concentrations of cocaethylene than would intravenous or smoked administration. We, therefore, compared the effects of route of cocaine administration on the formation and elimination of cocaethylene. Six experienced cocaine users were tested in 6 sessions, approximately 1 week apart. Deuterium-labeled cocaine (d(5)) was administered in all conditions. Oral cocaine-d(5) 2.0 mg/kg, intravenous cocaine-d(5) 1.0 mg/kg, and smoked cocaine-d(5) (200 mg) were administered after oral ethanol 1.0g/kg or placebo. A small, intravenous dose of deuterated cocaethylene (d(3)) also was administered with all conditions for determination of cocaethylene formation. Physiologic and subjective effects were recorded and plasma cocaine-d(5), cocaethylene-d(5), cocaethylene-d(3), and benzoylecgonine-d(5) were measured by gas chromatography-mass spectrometry. About 24% (+/- 11) of intravenous cocaine was converted to cocaethylene. The oral route (34% +/- 20) was significantly greater than from the smoked route (18% +/- 11) and showed a trend toward significance for greater formation of cocaethylene compared to the intravenous route. Within each route, the cocaine-ethanol combination produced greater increases in heart rate and rate-pressure product than cocaine alone. Global intoxication effects across time after smoking or intravenous administration were significantly greater when cocaine and ethanol were both given. Administration of cocaine by different routes alters the amount of cocaethylene formed through hepatic first-pass effects. Increased cardiovascular and subjective effects might explain the toxicity and popularity of the combined drugs.