Induction of propranolol metabolism by the azo dye sudan III in rats.
Effects of the azo dye sudan III, an inducer of cytochrome P450 isozymes belonging to the CYP1A subfamily, on propranolol (PL) in vitro and in vivo metabolism were investigated in rats. The kinetic parameters of the activity for each metabolic pathway were determined in liver microsomes from control and sudan III-treated rats. Sudan III pretreatment increased extensively PL 4-hydroxylase, 5-hydroxylase and N-desisopropylase activities at high but not at low PL concentrations. On the other hand, kinetic parameters of 7-hydroxylase activity were not affected by sudan III pretreatment. Sudan III pretreatment decreased blood concentrations of PL after intraportal infusion of PL at high doses (12.5 and 20 mg/kg), but not at a low dose (5 mg/kg). These observations were consistent with data obtained from the in intro studies showing that sudan III pretreatment induced low-affinity but not high-affinity cytochrome P450 isozymes involved in PL metabolism in rat liver microsomes.
Ishida
R
R
Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Obara
S
S
Masubuchi
Y
Y
Narimatsu
S
S
Fujita
S
S
Suzuki
T
T
D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects*; D006900:Hydroxylation; D007527:Isoenzymes / Q000096:biosynthesis; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D010088:Oxidoreductases / Q000096:biosynthesis; D011433:Propranolol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D013194:Staining and Labeling
D001391:Azo Compounds; D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D011433:Propranolol; D010088:Oxidoreductases; C034708:propranolol N-desisopropylase; C033006:sudan III