The effect of ageing on cytochrome p450 enzymes: consequences for drug biotransformation in the elderly.
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.
Wauthier
V
V
Unité PMNT, Ecole de Pharmacie, Université catholique de Louvain. 73, avenue E. Mounier, 1200 Bruxelles, Belgium.
Verbeeck
R K
RK
Calderon
P Buc
PB
D000367:Age Factors; D000368:Aged; D000818:Animals; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D012737:Sex Factors
D007527:Isoenzymes; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System