イプロニアジドの体内動態並びにフリーラジカル中間代謝物に及ぼすアスコルビン酸の影響

概要

論文の詳細を見る
The effects of ascorbic acid (AA) on the metabolic fate of iproniazid (IPN) and on the free radical intermediates derived from IPN were investigated in rats. After oral administration of IPN with or without AA, the plasma concentration and the urinary excretion of IPN and its metabolites were determined by gas chromatography-mass spectrometry using stable isotope labeled compounds as internal standards. In the excretion of IPN and its metabolites except hydrazine (Hy), the differences between co-administration and single administration were not observed. The excretion of Hy, which is a known hepatotoxic metabolite, decreased clearly in the co-administration of IPN and AA. When IPN and AA were co-administered orally, the profiles of plasma levels of IPN and its metabolites were almost similar after the administration of IPN alone. Furthermore, no differences between i.v. co-administration and i.v. administration alone were observed. These results indicated that AA did not affect both absorption and metabolism of IPN. By the electron spin resonance (ESR) spectroscopy and spin-trapping technique, the ESR signals due to the α-(4-pyridyl l-oxide)-N-tert-butylnitrone (4-POBN) adducts induced by isopropylhydrazine (IP-Hy) were two-fold higher than those by IPN in microsomal systems. The free radical formations of IPN and IP-Hy were significantly inhibited by AA in a dose dependent manner. The 4-POBN-trapped radical species generated from IPN and IP-Hy were presumed to be an isopropyl radical by the results of mass spectrometry. By the addition of an inhibitor of cytochrome P-450 such as SKF 525-A, the generation of the radicals derived from IPN and IP-Hy decreased, indicating that the radicals are formed by cytochrome P-450-dependent microsomal systems. In vivo experiments, the radical generations after i.p. administration of IPN with AA were significantly depressed in the plasma and liver, compared with those after the administration of IPN alone. On the basis of these results, it was suggested that AA may reduce the IPN-induced hepatitis.
公益社団法人日本薬学会の論文
1992-12-25

イプロニアジドの体内動態並びにフリーラジカル中間代謝物に及ぼすアスコルビン酸の影響

スポンサーリンク

概要

著者

関連論文

スポンサーリンク