Drug metabolism enzyme induction

Mankowski, D.C. and Ekins, S. (2003) Prediction of human drug metabolizing enzyme induction. Curr. Drug Metab.,... 

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. 

E (1997) Mechanism of action of dietary chemoprotective agents in rat liver induction of phase I and II drug metabolizing enzymes and aflatoxin B1 metabolism . Carcinogenesis, 18 1729-38. 

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... 

Vigilance for drug-drug interactions is required because of the greater number of medications prescribed to elderly patients and enhanced sensitivity to adverse effects. Pharmacokinetic interactions include metabolic enzyme induction or inhibition and protein binding displacement interactions (e.g., divalproex and warfarin). Pharmacodynamic interactions include additive sedation and cognitive toxicity, which increases risk of falls and other impairments. 

Birkeland C (1997) Geographic differences in ecological processes on coral reefs. In Birkeland C (ed) Life and death on coral reefs. Chapman Hall, New York, pp 273-287 Bock KW, Lipp HP, Bock-Henniq BS (1990) Induction of drug-metabolizing enzymes by xenobi-otics. Xenobiotica 20 1101-1 111... 

Mills, J.B., Rose, K.A., Sadagopan, N., Sahi, J. and de Morais, S.M. (2004) Induction of drug metabolism enzymes and MDR1 using a novel human hepatocyte cell line. The Journal of Pharmacology and Experimented Therapeutics, 309, 303-309. 

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. 

Remmer, H. Induction of drug-metabolizing enzymes in the endoplasmic reticulum of the liver by treatment with drugs. German Med. Mont. (1968) 13 53-59. 

Kuzuya Y, Adachi T, Hara H, Anan A, Izuhara K, Nagai H (2004) Induction of drug-metabolizing enzymes and transporters in human bronchial epithelial cells by beclomethasone dipropionate. IUBMB Life 56(6) 355-359. 

The metabolic and clinical condition of the patient also plays a role The individual with good kidney and liver function will respond quite differently to a drug than the patient who is not able to detoxify or excrete the compound. The user of laboratory data must be aware of the possible occurrence of drug-mediated enzyme induction, biological variations in the rate of clearance and storage in depot areas (B24), and the genetic factors that play a role in the toxicity of a drug (L2). 

Induction of drug metabolizing enzymes by xenobiotics is an important factor in understanding variations in drug response. Drug-mediated increases in these... 

A different and opposite activity to drug enzyme inhibition is the process of enzyme induction. This simply means that when some drug metabolizing enzymes are exposed to drug substrate their amount increases. 

B) Induction of drug-metabolizing enzymes results in a decrease in concentrations of the object (original) drug, thus potentially reducing efficacy. 

C) Induction of drug-metabolizing enzymes frequently requires the synthesis of new enzyme protein and thus may not occur immediately upon introduction of the inducing agent. 

L A. When one inhibits the action of a drug-metabolizing enzyme (A), one would expect an increase instead of a decrease in drug concentrations, since less is being metabolized. Induction of an enzyme (B) would have the opposite effect, since there would be more enzyme available to metabolize the drug. 

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. 

Mitotane, being closely related to the organochlo-rine insecticides, shares its inductive effects on the fiver microsomal drug-metabolizing enzyme system, and its use may therefore alter the requirement for concomitantly administered drugs that are also metabolized by this pathway. 

Markowitz JS, Donovan JL, DeVane CL, et al. Effect of St. John s wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. J Am Med Assoc 2003 290 1500-1504. 

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