Kendall M J
Department of Medicine, Queen Elizabeth Hospital, Edgbaston, Birmingham, England.
Drugs. 1995 Sep;50(3):454-64. doi: 10.2165/00003495-199550030-00004.
Fixed dose antihypertensive combinations are being used increasingly in the management of hypertension. There are advantages and disadvantages of this form of therapy. The key aims are to: (i) achieve increased efficacy by using drugs that complement each other's actions; (ii) use low doses to minimise adverse effects; and (iii) provide a simple once daily regimen. Fixed dose combinations containing metoprolol have the advantage that beta-blockers are drugs for which there is most evidence that they are cardioprotective; metoprolol is the best documented beta-blocker in this context. The early combination of conventional release metoprolol and hydrochlorothiazide was inadequately investigated by modern standards, but proved well tolerated and effective in clinical practice. The introduction of the long acting metoprolol CR/ZOK (controlled release/zero order kinetics) produced a very satisfactory once daily preparation with no major pharmacokinetic interactions. The fixed dose combination of felodipine and metoprolol CR/ZOK has been well investigated. The two agents complement each other's actions and together provide very effective blood pressure control, cardioprotection and very good tolerability. A case can be made that this preparation more closely meets the requirements of an ideal antihypertensive than a single agent given alone.
固定剂量的抗高血压联合用药在高血压治疗中的应用日益广泛。这种治疗方式有其优缺点。其主要目标是：（i）通过使用相互补充作用的药物来提高疗效；（ii）采用低剂量以尽量减少不良反应；（iii）提供简单的每日一次用药方案。含有美托洛尔的固定剂量组合具有这样的优势，即β受体阻滞剂是有最多证据表明具有心脏保护作用的药物；在这方面，美托洛尔是记录最完备的β受体阻滞剂。按照现代标准，传统缓释美托洛尔与氢氯噻嗪的早期联合用药研究并不充分，但在临床实践中证明耐受性良好且有效。长效美托洛尔CR/ZOK（控释/零级动力学）的推出产生了一种非常令人满意的每日一次制剂，且无重大药代动力学相互作用。非洛地平与美托洛尔CR/ZOK的固定剂量组合已得到充分研究。这两种药物相互补充作用，共同提供非常有效的血压控制、心脏保护作用以及良好的耐受性。可以说，这种制剂比单独使用单一药物更符合理想抗高血压药物的要求。
