ELIMINATION KINETICS OF DISULFIRAM IN ALCOHOLICS AFTER SINGLE AND REPEATED DOSES
ELIMINATION KINETICS OF DISULFIRAM IN ALCOHOLICS AFTER SINGLE AND REPEATED DOSES
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DOI：
10.1038/clpt.1984.213
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发表时间：
1984-01-01
影响因子：
6.7
通讯作者：
LACOURSIERE, RB
中科院分区：
文献类型：
--
作者：
FAIMAN, MD;JENSEN, JC;LACOURSIERE, RB
在 15 名男性酗酒者单剂量口服 250 毫克双硫仑后，并在 12 个给药天后再次测定双硫仑消除动力学。计算了双硫仑、二乙基二硫代氨基甲酸酯 (DDTC)、二乙基二硫代氨基甲酸酯甲酯 (DDTC-Me)、二乙胺 (DEA) 和二硫化碳 (CS2) 的表观 t1/2 [半衰期]，结果分别为 7.3、15.5、22.1、13.9 和 8.9 小时。呼吸中 CS2 的消除 t1/2 为 13.3 小时。对于呼吸中的双硫仑、DDTC、DDTC-Me、DEA 和 CS2，单次或重复给药后达到最大血浆浓度的平均时间为 8-10 小时，而血浆 CS2 浓度在双硫仑后 5-6 小时达到峰值。单次和重复给药后，1 个给药间隔期间，22.4% 和 31.3% 的双硫仑通过呼吸消除。单次和重复给药后，尿液中双硫仑剂量的1.7%和8.3%以DDTC-葡萄糖苷酸形式消除，而DEA则占剂量的1.6%和5.7%。双硫仑及其代谢物的血浆水平存在明显的受试者间差异。这种变异性可能是双硫仑脂溶性、血浆蛋白结合差异或肠肝循环影响的结果。
Disulfiram elmination kinetics were determined in 15 male alcoholics after 250 mg disulfiram taken orally as a single dose and again after 12 dosing days. Apparent t1/2 [half lives] were calculated for disulfiram, diethyldithiocarbamate (DDTC), diethyldithiocarbamate-methyl ester (DDTC-Me), diethylamine (DEA) and carbon disulfide (CS2) and were found to be 7.3, 15.5, 22.1, 13.9 and 8.9 h, respectively. Elimination t1/2 for CS2 in breath was 13.3 h. Average time to reach maximal plasma concentration after either single or repeated doses was 8-10 h for disulfiram, DDTC, DDTC-Me, DEA and CS2 in breath, while plasma CS2 concentration peaked 5-6 h after disulfiram. After single and repeated dosing 22.4 and 31.3% of the disulfiram was eliminated in the breath during 1 dosing interval. In urine, 1.7% and 8.3% of the disulfiram dose was eliminated as DDTC-glucuronide after single and repeated dosing, while DEA accounted for 1.6% and 5.7% of the dose. There was marked intersubject variability in plasma levels of disulfiram and its metabolites. This variability may be the result of disulfiram lipid solubility, differences in plasma protein binding, or the effect of enterohepatic cycling.