Background

Metoprolol is recommended for therapeutic use in multiple cardiovascular conditions, thyroid crisis, and circumscribed choroidal hemangioma. A detailed systematic review on the metoprolol literature would be beneficial to assess all pharmacokinetic parameters in humans and their respective effects on patients with hepatic, renal, and cardiovascular diseases. This review combines all the pharmacokinetic data on metoprolol from various accessible studies, which may assist in clinical decision making.

Methodology

The Google Scholar and PubMed databases were searched to screen articles associated with the clinical pharmacokinetics of metoprolol. The comprehensive literature search retrieved 41 articles including data on plasma concentration–time profiles after intravenous and oral (immediate-release, controlled-release, slow-release, or extended-release) routes of administration, and at least one pharmacokinetic parameter was reported in all studies included.

Results

Out of 41 retrieved articles, six were after intravenous and 12 were after oral administration in healthy individuals. The oral studies depict a dose-dependent increase in maximum plasma concentration (C_max), time to reach maximum plasma concentration (T_max), and area under the concentration–time curve (AUC). Two studies were conducted in R- and S-enantiomers, in which one study reported the gender differences, depicting greater C_max and AUC among women, whereas in another study S-metoprolol was found to have higher values of C_max, T_max, and AUC in comparison with R-metoprolol. Results in different diseases depicted that after IV administration of 20 mg, patients with renal impairment showed an increase in clearance (CL) (60 L/h vs 48 L/h) compared with healthy subjects, whereas a decrease in CL (36.6 ± 7.8 L/h vs 48 ± 6.6 L/h) was seen in patients with hepatic cirrhosis at a similar dose. In comparison with a single oral dose following administration of 15 mg IV in three divided doses, patients having an acute myocardial infarction (AMI) showed an increase in C_max (823 nmol/L vs 248 nmol/L) at a steady state. Twenty different studies have reported significant changes in CL, C_max, and AUC of metoprolol when it is co-administered with other drugs. One study has reported a drug–food interaction for metoprolol but no significant changes were seen in the C_max and AUC.

Conclusion

This review summarizes all the pharmacokinetic parameters of metoprolol after pooling up-to-date data from all the studies available. The summarized pharmacokinetic data presented in this review can assist in developing and evaluating pharmacokinetic models of metoprolol. Moreover, this data can provide practitioners with an insight into dosage adjustments among the diseased populations and can assist in preventing potential adverse drug reactions. This review can also help avoid side effects and drug–drug interactions.

中文翻译：

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美托洛尔的临床药代动力学：系统评价

背景

美托洛尔被推荐用于多种心血管疾病、甲状腺危象和局限性脉络膜血管瘤的治疗。对美托洛尔文献进行详细的系统评价将有助于评估人类的所有药代动力学参数及其对肝、肾和心血管疾病患者的各自影响。这篇综述结合了来自各种可访问研究的美托洛尔的所有药代动力学数据，这可能有助于临床决策。

方法

搜索 Google Scholar 和 PubMed 数据库以筛选与美托洛尔临床药代动力学相关的文章。综合文献检索检索到 41 篇文章，包括静脉内和口服（速释、控释、缓释或缓释）给药途径后的血浆浓度-时间曲线数据，至少一项药代动力学参数在包括所有研究。

结果

在检索到的 41 篇文章中，有 6 篇是静脉注射后的，12 篇是口服后的。口服研究描述了最大血浆浓度 ( Cmax )、达到最大血浆浓度的时间 ( _Tmax )_和浓度-时间曲线下面积 (AUC)的剂量依赖性增加。对 R 和 S 对映异构体进行了两项研究，其中一项研究报告了性别差异，描述了女性中更大的C _max和 AUC，而在另一项研究中发现 S-美托洛尔具有更高的C _max、T _{max 值}, 和 AUC 与 R-美托洛尔的比较。不同疾病的结果表明，与健康受试者相比，IV 给药 20 mg 后，肾功能不全患者的清除率（CL）增加（60 L/h vs 48 L/h），而 CL 减少（36.6 ± 7.8 L/h vs 48 ± 6.6 L/h）在肝硬化患者中观察到相似剂量。与分三次静脉注射 15 mg 后的单次口服剂量相比，患有急性心肌梗死 (AMI) 的患者在稳定状态下显示C _max增加（823 nmol/L 对 248 nmol/L）。20 项不同的研究报告了 CL、C _max、与其他药物合用时美托洛尔的 AUC 和 AUC。一项研究报告了美托洛尔的药物-食物相互作用，但C _max和 AUC没有显着变化。

结论

本综述汇总了所有可用研究的最新数据，总结了美托洛尔的所有药代动力学参数。本综述中总结的药代动力学数据有助于开发和评估美托洛尔的药代动力学模型。此外，这些数据可以让从业者深入了解患病人群的剂量调整，并有助于预防潜在的药物不良反应。该审查还可以帮助避免副作用和药物-药物相互作用。