KINETICS OF COMBINED DRUG-ACTION

For the purpose of obtaining quantitative concentration-effect relatio nship for combined drugs, rationales of the Hill equation were inferre d and five models, i.e., normal distribution (NRD), derivative of R (D RV), vacancy-dependent binding (VDB), equiresponse (EQR), and independ ence (IND), were proposed to estimate the intensity of the combined dr ug action. In conclusion, we could not come up to the unique concentra tion-effect relationship. Among the five models, the EQR, NRD, and VDB models gave almost identical response intensity. Discrimination of th ese three models is not of great importance. The DR V model gave a cha racteristic concave isobologram (overadditive), for a given ratio of H ill constants and independent of pharmacologic effect. In contrast, th e IND model was able to cope with convex isobolograms (underadditive).