RT Journal Article
SR Electronic
T1 Inhibition of Drug Metabolism
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 10
OP 14
VO 4
IS 1
A1 T. R. TEPHLY
A1 G. J. MANNERING
YR 1968
UL http://molpharm.aspetjournals.org/content/4/1/10.abstract
AB In a study employing hepatic microsomes from rats, estradiol-17β, testosterone, androsterone, progesterone, and hydrocortisone inhibited competitively the oxidation of ethylmorphine and hexobarbital. Inhibitor constants for each steroid were the same whether ethylmorphine or hexobarbital served as substrates. Results are consistent with the concept that certain drugs and steroids are alternative substrates for a common microsomal mixed function oxidase system. The inhibitory effects of steroids on chlorpromazine metabolism were both qualitatively and quanitatively different from those observed when ethylmorophine and hexobarbital metabolism were studied. Not only were the steroids less potent inhibitors of chlorpromazine oxidation, but inhibition was not competitive. ACKNOWLEDGMENTS This research was supported by USPHS grant No. GM-12543. Part of this material has appeared in abstract form (12). The authors gratefully acknowledge the able technical assistance of Mrs. Sheila Ham and Mrs. Shirley Green.