TY - JOUR T1 - Inhibition of Drug Metabolism JF - Molecular Pharmacology JO - Mol Pharmacol SP - 15 LP - 19 VL - 4 IS - 1 AU - R. E. STITZEL AU - T. R. TEPHLY AU - G. J. MANNERING Y1 - 1968/01/01 UR - http://molpharm.aspetjournals.org/content/4/1/15.abstract N2 - A number of structurally unrelated drugs are known to be metabolized by microsomal enzymes systems of such limited specificity that one drug will competitively inhibit the metabolism of another (1). However, of several drugs tested in in vivo studies, only codeine and ethylmorphine inhibiited hexobarbital metabolism (2). Drugs that inhibited in vitro, but not in vivo, conceivably failed in the latter case to reach effective concentrations at the metabolic site. The isolated perfused liver was used to circumvent this problem. Ethylmorphine, codeine, morphine, levomethorphan, dextromethorphan, chlorpromazine, and 2-diethylaminoethyl 2,2-diphenylvalerate (SKF 525-A) inhibited hexobarbital metabolism in the perfused liver. Some correlation was found between the inhibitor potency of a drug and the Michaelis constant (Km) for its own metabolism by hepatic microsomes. ACKNOWLEDGMENTS This research was supported by USPHS grant no. GM-12543. Part of this material appeared in abstract form (10). The authors gratefully acknowledge the able technical assistance of Mrs. Shirley Green. ER -