关键词: 联合 药物治疗, 药物相互作用, 药物协同作用, 药物拮抗作用, 药物剂量效应关系, 权重配方法

Abstract: Aim To show the performance of the weighted modification method in the clinical design of combination drug therapy. Methods A scheme combined by Drug1, Drug2 and Drug3 was used to treat infants with iron deficiency anemia for 2 wk in a hypothetical clinical trial. Thirty-six infants were randomly into 6 compound groups. Three drugs in the scheme were divided into 6 dose levels, which were evenly distributed to the 6 groups according to the weighted modification method. The increased Hb (△Hb) was recorded at 2, 3, 4 wk after the treatment (po). The dose-effect data at 4 wk were analyzed by the method, and then the doses in scheme were modified by the analytic result. The modified doses in the scheme would be further demonstrated.Results Drug1 and Drug2 were principal drugs, but Drug1 had larger contribution to the combined effect (△Hb) than Drug2. Drug3 had lttle effect. There was a strong synergism between Drug1 and Drug2 with the weighted coefficient (b1) =2. 636(P<0.05), and a slight synergism between Drug2 and Drug3 with bz =0.460 (P<0. 05). But there was a significant antagonism between Drug1 and Drug3 with the weighted cofficient(B) =-0.829 (P<0.05) 。The doses were adjusted to form a new scheme with Drug1 60 mg·kg^-1 +Drug2 10 mg·kg^-1(p) and Drug 3 was deleted from the scheme. The scheme was an optimal one confirmed by a demonstration trial.Conclusion This method is able to effectively determine important degree of drugs in combination, and to optimize their doses for designing the scheme of combination drug therapy.

Key words: combination drug therapy, drug combinations, drug interaction, program evaluation, drug dose-response relationship, weighted modification method