Billups S J, Carter B L
Kaiser Permanente, School of Pharmacy Practice, University of Colorado Health Sciences Center, Denver, USA.
Ann Pharmacother. 1998 Jun;32(6):659-71. doi: 10.1345/aph.17323.
To describe the pharmacology, pharmacokinetics, and clinical efficacy of mibefradil compared with other agents used for hypertension and angina.
A MEDLINE search was performed for the period of January 1980 through September 1997 using the key terms mibefradil or Ro 40-5967. All articles written in English were considered for review.
All clinical studies involving mibefradil were evaluated. Preclinical data were included if these data were not adequately represented in clinical (human) studies.
Mibefradil is the first member of a new class of calcium-channel antagonists (CCAs) that block the T-type calcium channels. A long elimination half-life makes once-daily dosing feasible, and the drug's lack of negative inotropy and reflex tachycardia distinguishes it from other available CCAs. When administered at recommended dosages (50 or 100 mg once daily), mibefradil reduces blood pressure over 24 hours in patients with hypertension, improves exercise capacity, and relieves anginal symptoms in patients with chronic stable angina pectoris.
Clinical studies have found that the antihypertensive effects of mibefradil are comparable with those of nifedipine, verapamil, and amlodipine, and more effective than those of diltiazem. These effects result from peripheral vasodilation and a slight reduction in heart rate. Selective vasodilation of the coronary vasculature makes it an effective antianginal agent when used alone or added to beta-blocker therapy. Mibefradil demonstrates no significant effects on cardiac contractility, and no adrenergic stimulation resulting in reflex tachycardia. Therefore, it may have some advantages over currently available CCAs, especially in patients with congestive heart failure, although such advantages are unproven in published clinical trials. Ongoing clinical studies, including the Mortality Assessment in Congestive Heart Failure Trial (MACH-1) currently in progress, are needed to clarify mibefradil's place in cardiovascular therapy.
描述米贝拉地尔与其他用于治疗高血压和心绞痛的药物相比的药理学、药代动力学及临床疗效。
使用关键词米贝拉地尔或Ro 40 - 5967对1980年1月至1997年9月期间的MEDLINE进行检索。所有英文撰写的文章均纳入综述范围。
对所有涉及米贝拉地尔的临床研究进行评估。若临床（人体）研究中未充分体现的临床前数据也纳入其中。
米贝拉地尔是一类新型钙通道拮抗剂（CCAs）中的首个成员，可阻断T型钙通道。其较长的消除半衰期使每日一次给药成为可能，且该药物缺乏负性肌力作用和反射性心动过速，这使其有别于其他现有的CCAs。当以推荐剂量（每日一次50或100毫克）给药时，米贝拉地尔可在24小时内降低高血压患者的血压，提高运动能力，并缓解慢性稳定性心绞痛患者的心绞痛症状。
临床研究发现，米贝拉地尔的降压效果与硝苯地平、维拉帕米和氨氯地平相当，且比地尔硫䓬更有效。这些作用源于外周血管舒张和心率略有降低。冠状动脉血管的选择性舒张使其单独使用或与β受体阻滞剂联合使用时成为有效的抗心绞痛药物。米贝拉地尔对心脏收缩力无显著影响，也无导致反射性心动过速的肾上腺素能刺激。因此，它可能比现有的CCAs具有一些优势，尤其是在充血性心力衰竭患者中，尽管这些优势在已发表的临床试验中尚未得到证实。需要进行正在进行的临床研究，包括目前正在进行的充血性心力衰竭死亡率评估试验（MACH - 1），以明确米贝拉地尔在心血管治疗中的地位。
