Biollaz J, Shaheen O, Wood A J
Clin Pharmacol Ther. 1985 Jun;37(6):665-8. doi: 10.1038/clpt.1985.108.
Ethmozine, a phenothiazine antiarrhythmic, is effective in atrial and ventricular arrhythmias. Because of the extensive hepatic metabolism of ethmozine, we investigated the effects of the potent hepatic enzyme inhibitor cimetidine on the kinetics and dynamics of ethmozine. Eight healthy men 22 to 40 years old (means = 27.6 years) received a single, oral, 500 mg dose of ethmozine. Ethmozine dosing was repeated 15 days later after cimetidine, 300 mg four times a day for 7 days. Plasma samples were drawn over the next 24 hours for measurement of ethmozine. ECGs were obtained 1, 2, 4, 8, and 24 hours after each dose. After cimetidine, ethmozine clearance fell from 38.2 +/- 10.7 to 19.7 +/- 4.2 ml/kg/min and the t1/2 increased from 3.3 +/- 1.3 to 4.6 +/- 1.6 hours. Ethmozine prolonged the PR and QRS intervals, but there was no detectable further increase after cimetidine. Heart rate and blood pressure were not altered by ethmozine either alone or in the combination. We conclude that cimetidine increases plasma concentrations of ethmozine but did not induce any detectable further increase in the PR or QRS intervals.
乙吗噻嗪是一种吩噻嗪类抗心律失常药物，对房性和室性心律失常均有效。由于乙吗噻嗪在肝脏的代谢广泛，我们研究了强效肝酶抑制剂西咪替丁对乙吗噻嗪动力学和药效学的影响。8名年龄在22至40岁（平均27.6岁）的健康男性单次口服500毫克乙吗噻嗪。15天后，在服用西咪替丁（每日4次，每次300毫克，共7天）后重复给予乙吗噻嗪。在接下来的24小时内采集血浆样本以测定乙吗噻嗪。每次给药后1、2、4、8和24小时记录心电图。服用西咪替丁后，乙吗噻嗪的清除率从38.2±10.7降至19.7±4.2毫升/千克/分钟，半衰期从3.3±1.3小时增加至4.6±1.6小时。乙吗噻嗪可延长PR和QRS间期，但服用西咪替丁后未发现进一步增加。单独使用乙吗噻嗪或联合使用时，心率和血压均未改变。我们得出结论，西咪替丁可增加乙吗噻嗪的血浆浓度，但未导致PR或QRS间期出现任何可检测到的进一步增加。
