Combination therapy for treatment of multi-drug resistant bacterial infections is becoming common. In vitro testing of drug combinations under realistic pharmacokinetic conditions is needed before a corresponding combination is eventually put into clinical use. The current standard for design of such in vitro simulations for drugs with different half-lives is heuristic and limited to two drugs. To address that void, we develop a rigorous design method suitable for an arbitrary number of $N$ drugs with different half-lives. The method developed offers substantial flexibility and produces novel designs even for two drugs. Explicit design equations are rigorously developed and are suitable for immediate use by experimenters. These equations were used in experimental verification using a combination of three antibiotics with distinctly different half-lives. In addition to antibiotics, the method is applicable to any anti-infective or anti-cancer drugs with distinct elimination pharmacokinetics.

用于治疗多重耐药性细菌感染的联合疗法正变得普遍。在相应的组合最终投入临床使用之前，需要在现实的药代动力学条件下对药物组合进行体外测试。目前针对具有不同半衰期的药物进行此类体外模拟设计的标准是启发式的，并且仅限于两种药物。为了解决这个空白，我们开发了一种适用于任意数量的严格设计方法$否$半衰期不同的药物。所开发的方法提供了极大的灵活性，即使对于两种药物也能产生新颖的设计。明确的设计方程式经过严格开发，适合实验者立即使用。这些方程式用于实验验证，使用三种半衰期截然不同的抗生素的组合。除抗生素外，该方法适用于任何具有明显消除药代动力学的抗感染或抗癌药物。