Induction of hepatic drug metabolizing enzyme

Hodgson E, Kulkarni AP, Fabacher DL, et al. 1980. Induction of hepatic drug metabolizing enzymes in mammals by pesticides A review. J Environ Sci Health B 15(6) 723-754. 

The reduction in therapeutic effectiveness that can occur when antihistamines are given for long periods is probably related to an induction of hepatic drug-metabolizing enzymes. Children tend to eliminate antihistamines more rapidly than adults, while individuals with hepatic impairment may eliminate them more slowly. 

In the rodent, frequently a dose-related increase of the liver weight paralleled by hepatocytic hypertrophy occurs. This phenomenon is often due to induction of hepatic drug metabolizing enzymes. It is obviously over-expressed in the rodent species with the aim to faster metabolise xenobiotics and also degradation... 

Heinrich-Hirsch B, Beck H, Chahoud 1, et al. 1997. Tissue distribution, toxicokinetics and induction of hepatic drug metabolizing enzymes in male rats after a single s.c. dose of 3,4,3, 4 -tetrachlorobiphenyl (PCB-77). Chemosphere 34(5-7) 1523-1534. 

Drug Interactions Barbiturates combine with other CNS depressants to cause severe depression ethanol is the most frequent offender, and interactions with first-generation antihistamines also are common. Isoniazid, methylphenidate, and monoamine oxidase inhibitors also increase the CNS-depressant effects. Other prominent drag interactions occin as a result of the induction of hepatic drug-metabolizing enzymes by barbiturates see above). 

H. Suzuki, F. Kishida, and J. Miyamoto, Induction of hepatic drug metabolizing enzymes and mutagens-activation capacity in several animal species, J. Pesticide Sci. 2, 421-426... 

The hepatic and renal toxicities of chloroform are selectively modified by induction of the drug-metabolizing enzyme systems in those organs (ref. 39) and the production of phosgene is strongly indicated (ref. 40). 

Kato R, Chiesara E, Frontino G. 1961. Induction of hepatic carisoprodol-metabolizing enzyme by pretreatment with some neuropsychotropic drugs in rats. Jpn. J. Pharmacol. 11 31-36... 

Verapamil, diltiazem, and perhaps nicardipine (but not nifedipine) inhibit hepatic drug-metabolizing enzymes. Metabolism of diltiazem, nifedipine, verapamil, and probably other calcium channel blockers subject to induction and inhibition. 

Siess, M.H. et al., Time course of induction of rat hepatic drug-metabolizing enzyme activities following dietary administration of flavonoids, J. Toxicol. Envimn. Health, 49, 481, 1996. 

Schoket B and Vincze I (1990) Dose-related induction of rat hepatic drug-metabolizing enzymes by diuron and chlorotoluron, two substituted phenylurea herbicides. Toxicology Letters 50 1-7. 

Inoue S. Simultaneous high-performance liquid chromatographic determination of 6 beta-hydroxycortisol and cortisol in urine with fluorescence detection and its application for estimating hepatic drug-metabolizing enzyme induction. J Chromatogr B Biomed Appl 1994 661 15-23. 

Rifamycin is found to afford induction of the specific hepatic drug-metabolizing enzyme system and, therefore, accelerates the metabolism of digitoxin, methadone, phenytoin, 3-blockers, verapamil, oral contraceptives, chloramphenicol, theophylline, besides—oral anticoagulants, estrogens, tolbutamide, barbiturates and itself... 

Guyan et al. 1990) have used several markers of lipid peroxidation (9-cis-, 11-tmns-isomer of linoleic acid, conjugated dienes and ultraviolet fluorescent products) to demonstrate significant increases in the duodenal aspirate after secretin stimulation in patients with acute and clinic pancreatitis. They interpreted this as indicating induction of hepatic and pancreatic drug-metabolizing enzymes in the face of a shortfidl of antioxidant defences, more marked in chronic pancreatitis. Subsequent studies in patients with chronic pancreatitis have confirmed decreased serum concentrations of selenium, -carotene and vitamin E compared with healthy controls (Uden et al., 1992). Basso aol. (1990) have measured increases in lipid peroxides in the sera of patients with chronic... 

The plasma clearance of theophylline varies widely. Theophylline is metabolized by the liver, so typical doses may lead to toxic concentrations of the drug in patients with liver disease. Conversely, clearance may be increased through the induction of hepatic enzymes by cigarette smoking or by changes in diet. In normal adults, the mean plasma clearance is 0.69 mL/kg/min. Children clear theophylline faster than adults (1-1.5 mL/kg/min). Neonates and young infants have the slowest clearance (see Chapter 59). Even when maintenance doses are altered to correct for the above factors, plasma concentrations vary widely. 

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