潰瘍の軽減を目的とした抗炎症薬フルルビプロフェンキメラドラッグの合成とin vivo評価

抄録

The antiinflammatory effect, gastrotoxicity and in vivo absorption property of chimera drug of flurbiprofen(FP)with histamine H₂-antagonist, PPA, were compared with those of FP and FP methyl ester. FP-PPA chimera drug and FP methyl ester were little hydrolyzed in the buffer of the pH 1.2 to 7.4 region in the absence or presence of pepsin and trypsin, in contrast to fast hydrolysis(t_1/2 : about 20 sec)in rat plasma. FP chimera drug inhibited carrageenin induced paw swelling in the same level as FP alone. FP-PPA chimera drug significantly reduced gastrotoxicity in comparison to equivalent dose of FP, whereas the coad-ministration of FP with PPA did not affect gastrotoxicity of FP. FP methyl ester caused slightly less damage to the gastric mucosa than FP alone. The plasma concentration of FP after administration of FP derivatives were similar to FP alone. These data suggested that chimera drug is effective for reduction of gastric damage, compared with either FP or alkyl ester prodrug like methyl ester.