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The Effect of Ageing on Cytochrome P450 Enzymes: Consequences for Drug Biotransformation in the Elderly

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Abstract:

Ageing is an aggravating factor leading to alterations in the biotransformation of drugs, and therefore their therapeutic efficacy and safety. In this review we discuss the influence of ageing on drug metabolizing enzymes in male Wistar rats. We report that drug metabolizing enzymes can be affected by ageing either by post-translational modifications or by transcriptional modifications. The post-translational modifications could be due to an increase of oxidative stress during ageing. Although it is now well established that transcriptional modifications are due to a change in the GH secretion profile in senescent rats, the intracellular mechanisms underlying these modifications are still unclear. In addition to the strong decrease in the activity of the main CYPs of male rats, we discuss the potential consequences on human drug metabolism in the elderly.

Keywords: Ageing; cytochrome P450; drug metabolism; growth hormone

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986707780090981

Affiliations: Unite PMNT, Ecole de Pharmacie, Universite catholique de Louvain. 73, avenue E. Mounier,1200 Bruxelles, Belgium.

Publication date: March 1, 2007

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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