Factors Affecting Drug Metabolism

Low level activation of MPS Interleukin-I Amyloidosis Hyperplastic liver foci Altered stem cell kinetics Altered drug metabolism Altered response to drugs C Biotechnics For biotechnics (and specifically monoclonal antibodies), factors affecting safety include... 

A biologically important factor affecting drug absorption is drug metabolism or reaction coincident with diffusion across a membrane. The reaction often produces inactive or less potent products than the parent drug. It is conceivable that the reaction will also reduce the drug flux into the systemic circulation. We are interested in the effect of reaction on membrane diffusion. 

Factors that affect drug metabolism will influence the development of serious adverse effects. TPMT, one of the three enzymes that metabolize 6-MP, is encoded by a gene on chromosome 6 that contains functional polymorphisms. Multiple variants have been described ( 2, 3A, 3B, 3C, 3D, 4, 5, 6, 7, 10 31,32) that result in lower TPMT activity, leading to preferential metabolism of 6-MP by the HGPRT enzyme. This results in an increase in the amount of cytotoxic thioguanine nucleotides and greater myelotoxicity. There appears to be an allele dose-dependent... 

Where drug are shown to form reactive intermediates by specific enzyme systems, it might be expected that the polymorphism or absence of these systems would track idiosyncratic reactions but to date no such link has been established. In fact, the most confounding element of idiosyncratic reactions is their unpredictable nature and whilst reactive intermediates may present a risk factor the true nature of the response is likely to be multifactorial. Changes in dmg metabolizing capacity, affecting the balance of bioactivation and bioinactivation processes which may be mediated through concomitant infection may also be a contributory factor. 

The apparent variable effect of age on drug metabolism is probably due to the fact that age is only one of many factors that affect drug metabolism. For example, cigarette smoking, alcohol intake, dietary modification, drugs, viral illness, caffeine intake, and other unknown factors also affect the rate of drug metabolism. 

Some people are rapid metabolizers of drugs and some are slow metabolizers. Factors that can affect the response to drugs... 

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