Factors affecting drug metabolism

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Metabolic systems

A key metabolic system found in the liver is known as the mixed function oxidase system. The enzyme involved, cytochrome P450, is induced by the presence of one or more of the drugs it metabolizes. This means that consistent exposure to drugs metabolized by P450 will increase the rate of metabolism and result in ever-increasing doses being required to have a therapeutic effect. An example of this is the drug phenobarbital, used for controlling epileptic seizures. Other drugs affected by P450 would also be metabolized more quickly, so the dose rate of these would also have to be increased.

Drug interaction

Other enzyme systems are not induced by the presence of the drugs they metabolize, resulting in a fixed amount of enzyme available at any one time. If two or more drugs are administered that use the same enzyme system, this can cause a delay in drug metabolism, resulting in drug toxicity if the dose of the drugs involved is not reduced.

Some drugs cause the inhibition of certain enzymes, which could result in the metabolism of that drug, or another drug, being slowed. Inadequate liver function can also have an effect of drug metabolism, as production of the necessary enzymes may be impaired. This could be due to disease but it should be borne in mind that neonatal and geriatric animals may also have reduced liver function.

Species variation

Species variation must also be taken into account when considering drug metabolism. Most notably, cats do not possess the ability to conjugate certain drugs and so elimination from the body is slowed. This increases the likelihood of toxicity in this species from drugs that are well tolerated in other species.

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