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活性炭和抗生素对纳多洛尔消除的增强作用。

Enhancement of nadolol elimination by activated charcoal and antibiotics.

作者信息

du Souich P, Caillé G, Larochelle P

出版信息

Clin Pharmacol Ther. 1983 May;33(5):585-90. doi: 10.1038/clpt.1983.79.

Abstract

This study was carried out to assess whether nadolol undergoes enterohepatic circulation. Eight healthy subjects received 80 mg nadolol orally on three occasions at least 2 wk apart. The first experiment was a control. The second consisted of nadolol followed in 3 hr by 3 gm activated charcoal given over a 9-hr period. In the third, the subjects received 0.5 gm erythromycin base and 0.5 gm neomycin four times a day orally for 2 days before nadolol. After the activated charcoal, the nadolol AUC fell from 2455 +/- 155 to 1355 +/- 123 ng . hr/ml (mean +/- SE), as did the percentage nadolol recovered in urine (15.4 +/- 1.4 to 10.2 +/- 0.7%) and the nadolol t1/2 (17.3 +/- 1.7 to 11.8 +/- 1.6 hr). These data suggest that nonrenal elimination increased. After the antibiotics, nadolol AUC was constant, percentage of nadolol recovered in urine fell to 12.7 +/- 1.7%, nadolol t1/2 fell to 11.6 +/- 1.3 hr, and mean peak nadolol concentration rose from 146 +/- 15 to 397 +/- 52 ng/ml. These results suggest that there is an enterohepatic circulation for nadolol, that activated charcoal may decrease nadolol bioavailability, and that antibiotics may increase the nadolol effect.

摘要

本研究旨在评估纳多洛尔是否会进行肠肝循环。八名健康受试者在至少间隔2周的三个不同时间口服80毫克纳多洛尔。第一次实验为对照实验。第二次实验是先服用纳多洛尔,3小时后在9小时内给予3克活性炭。第三次实验是在服用纳多洛尔前,受试者每天口服4次0.5克红霉素碱和0.5克新霉素,持续2天。服用活性炭后,纳多洛尔的曲线下面积(AUC)从2455±155降至1355±123纳克·小时/毫升(平均值±标准误),尿中回收的纳多洛尔百分比(从15.4±1.4降至10.2±0.7%)以及纳多洛尔的半衰期(从17.3±1.7降至11.8±1.6小时)也随之下降。这些数据表明非肾清除增加。服用抗生素后,纳多洛尔的AUC保持不变,尿中回收的纳多洛尔百分比降至12.7±1.7%,纳多洛尔半衰期降至11.6±1.3小时,纳多洛尔平均峰值浓度从146±15升至397±52纳克/毫升。这些结果表明纳多洛尔存在肠肝循环,活性炭可能会降低纳多洛尔的生物利用度,而抗生素可能会增强纳多洛尔的效果。

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