| The combination of drugs is a common practice for enhancing the efficiency of drug treatment, but selection of the optimal combination and the optimal doses remains a matter of trial and error.The present study was undertaken to evaluate the antinociceptive interaction between paracetamol (PAR) and ketoprofen (KPF). The effects of individual and fixed-ration combinations of orally given KPF and PAR were assayed in the mice writhing test and paw edema induced in the mice by injection of carrageenan into the sub-planta. Isobolographic analysis was employed to characterize the interaction type of KPF combined with PAR such as synergistic, additive and antagonistic. The effective dose that produced 50% antinociception (ED50) was calculated from the log dose-response curve of fixed ratio combinations of PAR with KPF. By isobolographic analysis, the ED50,mix was compared to the theoretical additive ED50,add As shown by isobolograms, KPF combined with PAR resulted in synergistic interactions and the experimental ED50,max was significantly smaller than the theoretically calculated ED50. The tree different rations between PAR and KPF also showed significantly synergistic interaction by isobolographic analysis. A pharmacokinetic character of the interaction between KPF and PAR was studied in plasma by using high-pressure liquid chromatography (HPLC). The mice received doses of 12 mg·kg-1 KPF and 36 mg·kg-1 PAR alone or in combination (n=6/group) orally. The pharmacokinetic events revealed that the combinations of KPF with PAR exerted synergistic (supra-additive) interaction have no concern with a pharmacokinetic interaction. Oedema was induced by...
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