Hepatic microsomal drug metabolizing

Campbell, M.A., S. Bandiera, L. Robertson, A. Parkinson, and S. Safe. 1983. Hepta-, hexa-, tetra- and dichloronaphthalene congeners as inducers of hepatic microsomal drug-metabolizing enzymes. Toxicology 26 193-205. 

PI. Peters, M. A., and Fonts, J. R., The influence of magnesium and some other divalent cations on hepatic microsomal drug metabolism in vitro. Biochem. Pharmacol. 19, 533-544 (1970). 

Induction of hepatic microsomal drug metabolizing enzymes. Additive central nervous system depression with other central nervous system depressants. 

Inhibits hepatic microsomal drug-metabolizing enzymes. (Ranitidine, famotidine, and nizatidine do not.) May inhibit the renal tubular secretion of weak bases. 

Inhibits hepatic microsomal drug-metabolizing enzymes. Inhibits aldehyde dehydrogenase. 

Induces hepatic microsomal drug metabolism. Susceptible to inhibition of metabolism by CYP2C9 and, to a lesser extent, CYP2C19. 

Inhibits hepatic microsomal drug-metabolizing enzymes. (Ranitidine, famotidine, and nizatidine do not appear to do so.) May inhibit the renal tubular secretion of weak bases. Purportedly reduces hepatic blood flow, thus reducing first-pass metabolism of highly extracted drugs. (However, the ability of cimetidine to affect hepatic blood... 

Beierschmitt, W. P, McNeish, J. D., Griffiths, 1C J., Nagahisa, A., Nakane, M. and Amacher, D. E. (2001) Induction of hepatic microsomal drug-metabolizing enzymes by inhibitors of 5-lipoxygenase (5-LO) studies in rats and 5-LO knockout mice. Toxicol Sci 63,15-21. 

St John s wort can cause drug interactions by inducing hepatic microsomal drug-metabolizing enzymes or the drug transporter P-glycoprotein, which causes a net efflux of substrates, such as amitriptyline, from intestinal epithelial cells into the gut lumen (SEDA-24,12). In 12 patients (9 women, 3 men) the addition of St John s wort 900 mg/ day to amitriptyline 150 mg/day led to a 20% reduction in plasma amitriptyline concentrations, while nortriptyline concentrations were almost halved (210). 

Phenytoin induces hepatic microsomal drug-metabolizing enzymes and thus reduces concentrations of haloperidol (663,664), thioridazine (664), and tiotixene (665). In two patients phenytoin reduced plasma clozapine concentrations and worsened psychosis (666). 

Adaptive Enzyme Theory. The aliesterases are largely found in the microsomes of rat liver cells (44). Recently Hart and Fouts (51,52, 67-69) have presented evidence that in vivo administration of chlordan or chemically related DDT stimulates the activity of hepatic microsomal drug-metabolizing enzymes, as evidenced by proliferation of smooth-surfaced endoplasmic reticulum (SER) which was first noted with phenobarbital. Several reviews of hepatic drug metabolism... 

The metabolism of quinidine is enhanced by drugs that induce hepatic microsomal drug-metabolizing enzymes (67), such as rifampicin (77) and phenytoin and pheno-barbital (78). This leads to an increase in the first-pass metabolism of quinidine, and thus increased requirements of oral quinidine but little change in intravenous dosages. 

Di Augustinem, R.R and J.R. Foutsm. 1969. The effects of unsaturated fatty acids on hepatic microsomal drug metabolism and cytochrome P-450. Biochem.. 115 ... 

Barbiturates induce hepatic microsomal drug-metabolizing enzymes resulting in an increased degradation of barbiturates, ultimately leading to barbiturate tolerance. 

Burmaster, S.D., Hook, R.H., Reith, M.K. and Cheng, L.K. (1995) Metabolism of terfenadine associated with CYP3A4 activity in human hepatic microsomes. Drug Metabolism and Disposition The Biological Fate of Chemicals, 23, 631-636. 

Ivanetich KM, Lucas S, Marsh JA. 1978. Organic compounds. Their interaction with and degradation of hepatic microsomal drug-metabolizing enzymes in vitro. Drug Metab Dispos 6 218-225. 

Kato Y, Haraguchi K, Kawashima M, et al. 1995. Induction of hepatic microsomal drug-metabolizing enzymes by methylsulphonyl metabolites of polychlorinated biphenyl congeners in rats. Chem Biol Interact 95 257-268. 

Phenobarbital induces hepatic microsomal drug-metabolizing enzymes. The sudden withdrawal of phenobarbital may precipitate withdrawal seizures. Therefore, the doses should be tapered gradually whenever discontinuation is contemplated. 

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