Koizumi T, Kakemi M, Katayama K
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
J Pharmacokinet Biopharm. 1993 Oct;21(5):593-607. doi: 10.1007/BF01059116.
For the purpose of obtaining quantitative concentration-effect relationship for combined drugs, rationales of the Hill equation were inferred and five models, i.e., normal distribution (NRD), derivative of R (DRV), vacancy-dependent binding (VDB), equiresponse (EQR), and independence (IND), were proposed to estimate the intensity of the combined drug action. In conclusion, we could not come up to the unique concentration-effect relationship. Among the five models, the EQR, NRD, and VDB models gave almost identical response intensity. Discrimination of these three models is not of great importance. The DRV model gave a characteristic concave isobologram (overadditive), for a given ratio of Hill constants and independent of pharmacologic effect. In contrast, the IND model was able to cope with convex isobolograms (underadditive).
为了获得联合用药的定量浓度-效应关系，推导了希尔方程的原理，并提出了五种模型，即正态分布（NRD）、R的导数（DRV）、空位依赖性结合（VDB）、等效反应（EQR）和独立性（IND），以估计联合药物作用的强度。总之，我们未能得出唯一的浓度-效应关系。在这五种模型中，EQR、NRD和VDB模型给出的反应强度几乎相同。区分这三种模型并不十分重要。对于给定的希尔常数比值且与药理效应无关，DRV模型给出了特征性的凹形等效应线图（超相加性）。相比之下，IND模型能够处理凸形等效应线图（次相加性）。
