Drug-metabolizing enzymes, inducers

Kuo C-H, Hook JB. 1982. Effects of drug-metabolizing enzyme inducers on cephaloridine toxicity in Fischer 344 rats. Toxicology 24 293-303. 

Cojocel C, Kramer W, Mayer D. Depletion of cytochrome P450and alterations in activities of drug metabolizing enzymes induced by cephaloridine in rat kidney cortex. Biochemical Pharmacol 1988 37(19) 3781-3785. 

Conney AH, Davison C, Gastel R, Burns JJ. 1960. Adaptive increases in drug-metabolizing enzymes induced by pheno-barbital and other drugs. J. Pharmacol. Exp. Ther. 130 1—8... 

Vij AG, Satija NK, Flora SJS. 1998. Lead induced disorders in hematopoietic and drug metabolizing enzyme system and their protection by ascorbic acid supplementation. Biomed Environ Sci 11 7-14. 

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. 

From investigations of the effect of emorfazone on liver drug-metabolizing enzymes, (3) has been classified as a phenobarbitone (phenobarbital)-type inducer of enzymes [65]. For results of clinical evaluations of emorfazone, see [66, 67],... 

Campbell MA, Gyorkos J, Leece B, et al. 1983. The effects of twenty-two organochlorine pesticides as inducers of the hepatic drug-metabolizing enzymes. Gen Pharmacol 14(4) 445-454. 

Lu, A.Y.H., Somogyi, A., West, S., Kuntzman, R., and Conney, A.H. Pregnenolone- 16a-carbonitrile A new type of inducer of drug-metabolizing enzymes. Arch. Biochem. Biophys. 

Because trimetrexate is metabolized by a P450 enzyme system, drugs that induce or inhibit this drug metabolizing enzyme system may elicit important drug interactions that may alter trimetrexate plasma concentrations, which include erythromycin, rifampin, rifabutin, ketoconazole, fluconazole, cimetidine, nitrogen substituted imidazole drugs (eg, clotrimazole, ketoconazole, miconazole). 

There are some clinically important pharmacodynamic drug-drug interactions to be mentioned. Antipsychotics will potentiate the central depressant effects of sedatives and of alcohol. They will also increase the risk of respiratory-depressant effects of opiates. Inducers of drug metabolic enzymes like for example rifampicin and several antiepileptics, may increase the elimination rate of antipsychotic agents and thus decrease their efficacy. 

Sustained-release formulations can produce stable serum concentrations with once or twice daily dosage. Therapeutic effects occur at blood levels > 5 mg/1, and side effects increase considerably at levels > 15 mg/1. Smoking, alcohol, anticonvulsants, and rifampicin induce the drug-metabolizing enzyme system in liver and reduce the half-life of theophylline. On the other hand, heart and liver failure, sustained fever, old age and drugs such as cimeti-dine, ciprofloxacin, and oral contraceptives reduce theophylline clearance and thereby increase serum concentrations. 

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. 

Oxcarbazepine is chemically and pharmacologically closely related to carbamazepine, but it has much less capacity to induce drug-metabolizing enzymes. This property decreases the problems associated with drug interactions when oxcarbazepine is used in combination with other drugs. The clinical uses and adverse effect profile of oxcarbazepine appear to be similar to those of carbamazepine. 

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