Amrein R, Hetzel W, Allen S R
Department of Clinical Research, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Eur J Anaesthesiol Suppl. 1995 Nov;12:5-11.
Combination therapy with two or more different drugs, with the intention of reaching the same therapeutic goal, was heavily criticized for a long time. However, it is accepted today, especially when advantages over monotherapy can be shown. For the induction of anaesthesia or for long-term sedation in the intensive care unit, combination therapy may offer an improved effect profile, a more balanced ratio of desired versus adverse effects, an improved time-course of effect, simpler treatment requirements or lower costs. Midazolam and propofol have been investigated as potential partners for those two indications. The mechanism of action, pharmacokinetic properties, pharmacological effect, the way in which they interact at the receptor site, the differences in pharmaceutical formulations, the side-effect profiles and economic considerations were compared. Animal experiments and clinical pharmacology studies have shown that midazolam and propofol have synergy with other centrally active drugs. It could be expected that the relationship between desired effects and adverse effects could be improved by skilful use of the synergism between midazolam and propofol. Co-induction of anaesthesia and co-administration in long-term sedation can offer improvements in therapeutic situations compared with monotherapy. These improvements are in terms of a more suitable effect profile, a more favourable ratio of desirable effects to side-effects, optimization of the time-course of effects and reduced costs.
长期以来，为达到相同治疗目标而联合使用两种或更多不同药物的联合疗法备受诟病。然而，如今它已被接受，尤其是当能证明其相较于单一疗法具有优势时。对于麻醉诱导或重症监护病房的长期镇静而言，联合疗法可能具有改善的效应特征、更平衡的预期效应与不良反应比例、更好的效应时程、更简单的治疗要求或更低的成本。咪达唑仑和丙泊酚已被作为这两种适应症的潜在联合用药进行研究。对它们的作用机制、药代动力学特性、药理作用、在受体部位的相互作用方式、药物制剂差异、副作用谱以及经济因素进行了比较。动物实验和临床药理学研究表明，咪达唑仑和丙泊酚与其他中枢活性药物具有协同作用。可以预期，通过巧妙利用咪达唑仑和丙泊酚之间的协同作用，有望改善预期效应与不良反应之间的关系。与单一疗法相比，联合诱导麻醉和长期镇静联合用药可改善治疗情况。这些改善体现在更合适的效应特征、更有利的预期效应与副作用比例、效应时程的优化以及成本降低。
