[Effects of ascorbic acid on the metabolic fate and the free radical formation of iproniazid].
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 alpha-(4-pyridyl 1-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Matsuki
Y
Y
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Hongu
Y
Y
Noda
Y
Y
Kiwada
H
H
Sakurai
H
H
Goromaru
T
T
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D016166:Free Radical Scavengers; D005609:Free Radicals / Q000378:metabolism; D007490:Iproniazid / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D016166:Free Radical Scavengers; D005609:Free Radicals; D007490:Iproniazid; D001205:Ascorbic Acid