Drug-enzyme interaction

Rifapentine is an analogue of rifampin that is active against M. tuberculosis and M. avium. Rifapentine s mechanism of action, cross-resistance, hepatic induction of P450 enzymes, drug interactions, and toxic profile are similar to those of rifampin. It has been used in the treatment of tuberculosis caused by rifampin-susceptible strains. 

Drug interactions The label states that no pharmacokinetic-based drug-drug interaction studies have been conducted with Synarel. However, because nafarelin acetate is a peptide that is primarily degraded by peptidase and not by cytochrome P-450 enzymes, drug interactions would not be expected to occur. 

The first chapter by Moszyliski presents in a systematic and comprehensive manner the current state-of-the-art theory of intermolecular interactions. Numerous examples illustrate how theoreticians and experimentalists working in tandem may gather valuable quantitative results related to intermolecular interactions, like accurate potential functions, interaction-induced properties, spectra and collisional characteristics or dielectric, refractive or thermodynamic properties of bulk phases. On the other hand the most advanced Symmetry Adapted Perturbation Theory (SAPT) enables validation of more approximate variation-pertubation models which could be applied to the analysis of specific interactions in much larger molecular systems, for example enzyme-drug interactions discussed in Chapter VIII by Berlicki et al. 

Other Test Items and Precautions. These examine the effects on drug metabolic enzymes, drug interaction and the first pass effect as required. In case of race-mates, the differences of pharmacokinetics between isomers should be examined by quantifying each isomer separately. 

Interactions with Cytochrome 450 Enzymes. Drug interactions with opioid analgesics can also result from their interaction withcyctochromep450 (CYP) isozymes, specifically 3A4 and 2D6 (Table 7.5) (50). 

Metabolism of Drugs and Other Foreign Compounds by Enzymatic Mechanisms 6,11 (1963) Dr. J. R. Gillette Head, Section on Enzymes Drug Interaction, Laboratory of Chemical Pharmacology, National Heart Institute, Bethesda 14, Maryland, USA... 

Drug Interactions During Metabolism Enzyme Inhibition... 

Following concurrent administration of two drugs, especially when they are metabolized by the same enzyme in the liver or small intestine, the metabolism of one or both drugs can be inhibited, which may lead to elevated plasma concentrations of the dtug(s), and increased pharmacological effects. The types of enzyme inhibition include reversible inhibition, such as competitive or non-competitive inhibition, and irreversible inhibition, such as mechanism-based inhibition. The clinically important examples of drug interactions involving the inhibition of metabolic enzymes are listed in Table 1 [1,4]. 

Drug Interactions. Table 1 Examples of clinically important drug interactions due to enzyme inhibition... 

Lewis, D. F., Lake, B. G., Ito, Y., Anzenbacher, P. Quantitative structure-activity relationships (QSARs) within cytochromes P450 2B (CYP2B) subfamily enzymes the importance of lipophilicity for binding and metabolism. Drug Metab. Drug Interact. 

Other assays for assessing CYP clearance are also employed, although often less widely or with lower compound throughput. Recombinant CYP enzymes allow the determination of the kinetic parameters for metabolism of individual compounds by individual CYPs. Recombinant CYPs also provide an avenue to assessing and understanding the potential for drug-drug interactions that may occur between two or more compounds. 

Use of zileuton is uncommon due to the need for dosing four times a day, potential drug interactions, and the potential for hepatotoxicity with the resulting need for frequent monitoring of liver enzymes. In patients started on zileuton, serum alanine aminotransferase concentrations should be monitored before treatment begins, monthly for the first 3 months, every 2 to 3 months for the remainder of the first year, and then periodically thereafter for as long as the patient continues to receive the medication. Zileuton also inhibits the cytochrome P-450 (CYP) mixed function enzyme system and has been shown to decrease the clearance of theophylline, R-warfarin and propranolol.34... 

Only a small number of drug interactions have been reported with donepezil. In vitro studies show a low rate of binding of donepezil to cytochrome P-450 (CYP)3A4 or 2D6. Whether or not donepezil has the potential for enzyme induction is not known. No interactions with theophylline, cimeti-dine, warfarin, digoxin, or ketoconazole have been documented. In vitro studies show that inhibitors of CYP3A4 and 2D6 have the potential to inhibit the metabolism of donepezil. The clinical relevance of this is unknown. However, monitoring for possible increased peripheral side effects is advised... 

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. 

Keto con azole Inhibits several 200 mg twice reactions develops with continued use. Hematologic disturbances and hypothyroidism also seen. Generally well High potential for drug interactions due to potent induction of hepatic enzymes. Effective in a majority of causes ... 

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