Enzyme Induction by Drugs

Abstract

SUMMARY The properties of the hepatic microsomal, drug detoxicating, enzyme system are reviewed with particular reference to its inducibility. Induction is modified by various factors of which the diet is particularly important. A theoretical model system for induction has been proposed and this is discussed. There are a number of methods for assessing microsomal enzyme induction in man, none of which is ideal. Nevertheless, induction is a well recognised phenomenon in man and has a bearing on the metabolism of a number of endogenous substances. The effect of induction on steroid metabolism and the relationship between inducers, vitamin D, and metabolic bone disease is discussed. Bilirubin metabolism is affected by changes in microsomal enzyme activity and inducers have been used therapeutically in some cases of hyperbilirubinaemia. The relationship between drugs and the hepatic porphyrias is reviewed. The hepatic microsomal enzyme system is but one of many inducible enzymes and the role of induction in general in metabolic regulation is emphasised.

Effect of caffeine -coconut products interactions on induction of microsomal drug-metabolizing enzymes in wistar albino rats

“…Thus, it seems that the decrease in ALT and AST activities enhanced the induction of microsomal drug-metabolizing enzymes, and these regulatory controls may act to conserve nutrients and energy for the cells. These results are in consonance with the studies of Orrhenuis et al (1965), Marshall (1978, Remmer and Merker (1993), and Singh et al (1998). The reports of these workers showed that increased protein synthesis due to increased glucuronidation of the endoplasmic reticulum and decreased permeability of the liver cells resulted in induction of the microsomal drugmetabolizing enzymes.…”

“…The Protein/RNA ratios are suggestive of enzyme induction and serum endoplasmic reticulum proliferation (Marshall, 1978;Hunter and chasseaud, 1978;Bertolini et al, 1980;Salem et al, 1981;Bahtnager and Misra, 1988;Singh et al, 1998). This is because microsomal enzyme induction could most likely depends on de novo protein biosynthesis (Bertolini et al, 1980;Rodwell, 1996;Coon, 1996;Singh et al, 1998).…”

Evaluation of cyclosporin‐phenytoin interaction with observations on cyclosporin metabolites.

“…However, since we found essentially no metabolite 17 or 18 in serum, the differences between RIA and h.p.l.c. (Gelehrter, 1976;Marshall, 1978). The enhanced clearance of antipyrine in the healthy subjects is also consistent with enzyme induction, but does not prove that phenytoin increased cyclosporin metabolism in these individuals.…”

Impaired enzyme induction by rifampicin in the elderly [letter]

“…Other investigators have reported enhancement of the metabolism of quinidine and theophylline by phenytoin in patients aged 65 years (Urbano, 1983;Kroboth et al, 1983). Since phenytoin and rifampicin appear to be more powerful enzyme inducing agents than dichloralphenazone (Gelehrter, 1976;Marshall, 1978), it seemed possible that differences in the enzyme inducing drugs might explain the apparent discrepancy.…”