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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Clinically important interaction between tedisamil and verapamil.
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Clinically important interaction between tedisamil and verapamil.

机译：泰地米尔和维拉帕米之间的临床重要相互作用。

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摘要

Tedisamil, a class III antiarrhythmic drug, is a P-glycoprotein substrate. Tedisamil treatment may implicate coadministration with class IV antiarrhythmics such as verapamil, a P-glycoprotein inhibitor. Pharmacokinetic and pharmacodynamic interactions between tedisamil and verapamil were evaluated in a double-blind, crossover study. Twelve healthy volunteers received a 3-day treatment of tedisamil (100 mg bid), verapamil (180 mg bid), a combination of these drugs, or placebo. Blood pressure and electrocardiograms were assessed daily and cardiac output and pharmacokinetics on day 3. Combination of tedisamil and verapamil increased tedisamil plasma concentrations (AUC(0-12 h): +77%, CI(90%): +51% to +108%; C(max): +78%, CI(90%): +57% to +102%) compared to tedisamil monotreatment but decreased plasma concentrations of verapamil (AUC(0-12 h): -21%, CI(90%): -32% to -8%; C(max): -28%, CI(90%): -39% to -14%) and norverapamil (AUC(0-12 h): -17%, CI(90%): -28% to -6%; C(max): -20%, CI(90%):-29% to -10%) compared to verapamil monotreatment. Compared to placebo, verapamil and the combination treatment increased PR by 23.5 (CI(95%): 17.9 to 29.2) ms and 12.2 (5.7 to 17.0) ms, respectively. Compared to placebo, tedisamil and the combination treatment increased QTc by 27.8 (15.8 to 39.8) ms and 45.7 (33.7 to 57.7) ms, respectively. Thus, concomitant use of tedisamil with P-glycoprotein inhibitors likely results in clinically significant drug interactions.
机译：Tedisamil是一种III类抗心律不齐药物，是一种P-糖蛋白底物。 Tedisamil的治疗可能与IV类抗心律不齐药物（例如P-糖蛋白抑制剂维拉帕米）共同给药。在一项双盲，交叉研究中评估了泰地米尔和维拉帕米之间的药代动力学和药效学相互作用。 12名健康志愿者接受了3天内的泰地米尔（100 mg bid），维拉帕米（180 mg bid），这些药物的组合或安慰剂的3天治疗。每天评估血压和心电图，并在第3天评估心输出量和药代动力学。联合使用tedisamil和verapamil会增加tedisamil血浆浓度（AUC（0-12小时）：+ 77％，CI（90％）：+ 51％至+108 ％; C（max）：+ 78％，CI（90％）：+ 57％至+ 102％）与泰地昔单抗相比，但维拉帕米的血浆浓度降低（AUC（0-12 h）：-21％，CI（ 90％）：-32％至-8％; C（最大值）：-28％，CI（90％）：-39％至-14％）和去甲拉帕米（AUC（0-12 h）：-17％，与维拉帕米单药治疗相比，CI（90％）：-28％至-6％; C（max）：-20％，CI（90％）：-29％至-10％）。与安慰剂相比，维拉帕米和联合治疗使PR分别增加23.5（CI（95％）：17.9至29.2）ms和12.2（5.7至17.0）ms。与安慰剂相比，泰地米尔和联合治疗使QTc分别增加27.8（15.8至39.8）ms和45.7（33.7至57.7）ms。因此，将替地米美与P-糖蛋白抑制剂并用可能会导致临床上显着的药物相互作用。

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