Metabolism drug interactions involving

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]. 

Many statins are metabolized by CYP3A4, and this and other mechanisms of drug interactions involving statins have been reviewed (69). Other drugs metabolized by CYP3A4 can greatly increase statin concentrations in the body and precipitate rhabdomyolysis. Although the statins are similar in their ability to lower cholesterol... 

So far, analysis has centered on metabolic drug interactions. But there are many pharmacokinetic interactions other than those occurring at enzymatic sites, such as those involving transporters or altered physiological function. 

One final consideration of drug interactions involving intestinal CYP3A is the fact that differential modulation of intestinal and hepatic CYP3A is possible. Simultaneous inhibition of intestinal first-pass metabolism and stimulation or induction of hepatic first-pass metabolism has been reported for the interaction between the herbal supplement echinacea (Echinacea purpurea root) and... 

Figure 1 Schematic representation of the mechanism of pharmacokinetic drug interactions. Plasma concentrations of the victim drug are determined by its dosing rate and metabolic clearance. Plasma levels, in turn, determine drug concentrations at the receptor site and ultimately its pharmacodynamic effect. A pharmacokinetic drug interaction involves the effect of the perpetrator on the metabolic clearance of the victim. When the perpetrator is an inducer, clearance of the victim is increased, plasma levels are diminished, and pharmacological effect is reduced. Conversely, when the perpetrator is an inhibitor, clearance of the victim is reduced, plasma levels are increased, and pharmacodynamic effect is enhanced.

Generally, only a few of the adverse drug interactions involving proton pump inhibitors are of clinical significance, but an awareness of all interactions is necessary as individual variations do occur. Metabolism involves CYP2C19 and CYP3A4, Individual proton pump inhibitors differ considerably in their potential for adverse drug interactions, which are due to ... 

Zhou-Pan XR, Seree E, Zhou XJ, Placidi M, Maurel P, Barra Y, Rahmani R. Involvement of human liver cytochrome P450 3A in vinblastine metabolism drug interactions. Cancer Res 1993 53(21) 5121-6. 

Environmental factors. Examples of these are co-administration of other drugs, which can affect the rate and extent of drug metabolism. This can become literally a matter of life and death as a number of potentially fatal drug interactions involve liver enzyme induction and competition for drug-metabolism enzymes. 

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