Befunolol代謝活性に関する検討還元活性を中心として

概要

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Befunolol was transformed to 11 metabolites along the following three major metabolic pathways by rabbit hepatic 9000×g supernatant : (i) reduction of 2-ketone・carbonyl ; (ii) 4-hydroxylation of benzofuran ring ; (iii) oxidation of 7-side chain. Only one metabolite (reduction product of befunolol ; MI) was formed after incubating befunolol with rabbit hepatic cytosol. The same liver fraction also converted MI to befunolol in the presence of NADP^+. The befunolol-reducing activity in the cytosol utilized NADPH more effectively than NADH. Optimum pH was approximately 7 and the apparent K_m value was 0.81 mM. The reducing activity was competitively inhibited by the presence of microsome, including other befunolol-metabolizing activities such as 4-hydroxylating activity. In hamsters, befunolol-4-hydroxylating activity varied remarkably by treatment with SKF 525-A, CCl_4 or phenobarbital, whereas the befunolol-reducing activity was little affected by the same treatment. In vivo formation of befunolol from MI was recognized in rabbits, rats and guinea pigs.
公益社団法人日本薬学会の論文
1980-04-25