Plosker G L, Clissold S P
Adis International Limited, Auckland, New Zealand.
Drugs. 1992 Mar;43(3):382-414. doi: 10.2165/00003495-199243030-00006.
Conventional formulations of metoprolol have become well established in cardiovascular medicine and are particularly useful in the management of hypertension and ischaemic heart disease. Recently developed controlled release metoprolol delivery systems (metoprolol CR/ZOK and metoprolol OROS) were designed to overcome the drug delivery problems of matrix-based sustained release forms by releasing the drug at a relatively constant rate over a 24-hour period, and thus producing sustained and consistent metoprolol plasma concentrations and beta 1-blockade while retaining the convenience of once daily administration. Clinically and statistically significant reductions in blood pressure have been observed with metoprolol CR/ZOK and metoprolol OROS 24 hours after administration in mildly or moderately hypertensive patients. Studies in patients with mild to moderate hypertension have demonstrated that a similar or higher percentage of patients achieved a goal response with metoprolol CR/ZOK compared with matrix-based sustained release formulations of metoprolol, or conventional atenolol or bisoprolol, while metoprolol OROS achieved an equal or greater response rate compared with conventional or matrix-based sustained release metoprolol preparations. In patients with stable effort angina pectoris, once daily administration of metoprolol CR/ZOK provided at least equal antianginal efficacy as conventional metoprolol in divided doses, while metoprolol OROS reduced the mean number of anginal attacks by the same margin as atenolol. Controlled release metoprolol formulations have been well tolerated in clinical trials. Metoprolol CR/ZOK was associated with a similar or lesser degree of adverse effects related to the central nervous system compared with atenolol or long acting propranolol. Metoprolol CR/ZOK also demonstrated less pronounced beta 2-mediated bronchoconstrictor effects than atenolol in asthmatics, and less general fatigue and leg fatigue in healthy subjects. Metoprolol OROS produced less pronounced bronchoconstrictor effects than atenolol, matrix-based sustained release metoprolol or long acting propranolol in patients with asthma or obstructive airways disease, and healthy volunteers. These results are presumably due to the beta 1-selectivity of metoprolol in addition to the relatively low plasma concentrations maintained by metoprolol CR/ZOK and metoprolol OROS, and the avoidance of high peak plasma concentrations with these agents. Despite the relative safety of the controlled release forms of metoprolol, the use of all beta-adrenoceptor antagonists should be avoided in patients with a history of bronchospasm. Thus, controlled release metoprolol formulations offer the potential to maximise the confirmed benefits of this agent in the management of hypertension and angina, by maintaining clinically effective plasma concentrations within a narrow therapeutic range over a 24-hour dose interval.
美托洛尔的传统剂型在心血管医学中已得到广泛应用，尤其在高血压和缺血性心脏病的治疗中非常有用。最近开发的美托洛尔控释给药系统（美托洛尔缓释片/佐剂和琥珀酸美托洛尔缓释片）旨在克服基于基质的缓释剂型的药物递送问题，通过在24小时内以相对恒定的速率释放药物，从而产生持续且一致的美托洛尔血浆浓度和β1受体阻滞作用，同时保留每日一次给药的便利性。在轻度或中度高血压患者给药24小时后，观察到美托洛尔缓释片/佐剂和琥珀酸美托洛尔缓释片可使血压出现具有临床和统计学意义的降低。对轻度至中度高血压患者的研究表明，与基于基质的美托洛尔缓释剂型、传统阿替洛尔或比索洛尔相比，使用美托洛尔缓释片/佐剂达到目标反应的患者比例相似或更高，而与传统或基于基质的美托洛尔缓释制剂相比，琥珀酸美托洛尔缓释片达到了相同或更高的反应率。在稳定型劳力性心绞痛患者中，美托洛尔缓释片/佐剂每日一次给药提供的抗心绞痛疗效至少与传统分次给药的美托洛尔相当，而琥珀酸美托洛尔缓释片使心绞痛发作的平均次数减少幅度与阿替洛尔相同。美托洛尔控释制剂在临床试验中耐受性良好。与阿替洛尔或长效普萘洛尔相比，美托洛尔缓释片/佐剂与中枢神经系统相关的不良反应程度相似或较轻。在哮喘患者中，美托洛尔缓释片/佐剂的β2介导的支气管收缩作用也比阿替洛尔轻，在健康受试者中引起的全身疲劳和腿部疲劳也较少。在哮喘或阻塞性气道疾病患者以及健康志愿者中，琥珀酸美托洛尔缓释片产生的支气管收缩作用比阿替洛尔、基于基质的美托洛尔缓释制剂或长效普萘洛尔轻。这些结果可能是由于美托洛尔的β1选择性，以及美托洛尔缓释片/佐剂和琥珀酸美托洛尔缓释片维持的相对较低血浆浓度，并且避免了这些药物出现高血浆峰浓度。尽管美托洛尔控释剂型相对安全，但有支气管痉挛病史的患者应避免使用所有β肾上腺素能拮抗剂。因此，美托洛尔控释制剂有可能通过在整个24小时给药间隔内将临床有效血浆浓度维持在狭窄的治疗范围内，使该药物在高血压和心绞痛治疗中已得到证实的益处最大化。
