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健康受试者中丙吡胺的胃肠透析

Gastrointestinal dialysis of disopyramide in healthy subjects.

作者信息

Arimori K, Kawano H, Nakano M

机构信息

Department of Pharmacy, Kumamoto University Hospital, Japan.

出版信息

Int J Clin Pharmacol Ther Toxicol. 1989 Jun;27(6):280-4.

PMID:2737797
Abstract

The effect of oral activated charcoal on the clearance of disopyramide was investigated in six healthy subjects. Oral administration of multiple doses of activated charcoal at 4, 6, 8 and 12 h after ingestion of the drug reduced the serum levels of both disopyramide and its main metabolite, mono-N-dealkyldisopyramide (MND). The mean serum level of disopyramide at 24 h after oral administration of the drug was significantly decreased from 0.22 in the control to 0.091 micrograms/ml by multiple doses of activated charcoal. The serum half-life and AUC0-infinity were decreased to 67% and 81%, respectively, and the apparent total body clearance was increased to 122% as compared with the control treatment. The apparent volume of distribution was not significantly different between both treatments. The cumulative amounts of urinary excretion of both disopyramide and MND with activated charcoal treatment were decreased as compared with those in the control treatment. Mean residence time (MRT) of disopyramide obtained from the serum data decreased from 7.8 (control) to 6.9 h (charcoal treatment) and the values were approximately consistent with those obtained from the urinary data. These results indicate that oral administration of activated charcoal would enhance the clearance of disopyramide in acute drug poisoning even after the drug has been absorbed into the systemic circulation from the g.i. tract.

摘要

在6名健康受试者中研究了口服活性炭对丙吡胺清除率的影响。在摄入药物后4、6、8和12小时多次口服活性炭可降低丙吡胺及其主要代谢产物单-N-去烷基丙吡胺(MND)的血清水平。口服该药物后24小时,丙吡胺的平均血清水平从对照组的0.22显著降至多次口服活性炭后的0.091微克/毫升。与对照治疗相比,血清半衰期和AUC0-∞分别降至67%和81%,表观全身清除率增至122%。两种治疗之间的表观分布容积无显著差异。与对照治疗相比,活性炭治疗的丙吡胺和MND的尿排泄累积量均减少。从血清数据获得的丙吡胺平均驻留时间(MRT)从7.8小时(对照)降至6.9小时(活性炭治疗),这些值与从尿数据获得的值大致一致。这些结果表明,即使药物已从胃肠道吸收进入体循环,口服活性炭仍可提高急性药物中毒时丙吡胺的清除率。

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