The effects of malotilate on hepatic drug metabolizing systems in different strains of rats.
1. In Sprague-Dawley (SD) rats treated for 7 days with malotilate (MAL:250 mg/kg, p.o.), cytochrome P-450 and b5 contents, aminopyrine N-demethylase and heme oxygenase activities were significantly increased. In Wistar rats, cytochrome b5 content and heme oxygenase and delta-aminolevulinic acid synthetase activities were found to be significantly increased. 2. Among the antipyrine metabolites excreted in urine during the 24 hr after antipyrine (100 mg/kg, i.p.) administration, norantipyrine increased significantly in Sprague-Dawley rats, while a significant increase of 4-hydroxyantipyrine was observed in Wistar rats. 3. The serum dimethadione/trimethadione ratio was only found to be significantly increased in Sprague-Dawley rats. 4. These results indicate that malotilate may have inducible effects on hepatic drug metabolizing enzymes, and that it affects the various cytochrome P-450 isozymes from different strains of rat in different ways.
Kai
K
K
Department of Pharmacology, School of Medicine, Showa University, Tokyo, Japan.
Kobayashi
S
S
Uchida
E
E
Sakai
H
H
Tanaka
E
E
Kurata
N
N
Yasuhara
H
H
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003573:Cytochrome b Group / Q000378:metabolism; D015786:Cytochromes b5; D004591:Electrophoresis, Polyacrylamide Gel; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008314:Malonates / Q000494:pharmacology*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013997:Time Factors
D003573:Cytochrome b Group; D008314:Malonates; D004364:Pharmaceutical Preparations; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D000469:Alkaline Phosphatase; C024808:diisopropyl 1,3-dithiol-2-ylidenemalonate