Problem #6
Explain the influence of aging on each of the
following:
Drug metabolism through CYP3A4 (consider both...
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Biology
Problem #6
Explain the influence of aging on each of thefollowing:
Drug metabolism through CYP3A4 (consider both gut and liver)
Glucuronidation
Sulfation
Acetylation
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Influence of ageing on Drug Metabolism through CYP3A4 in liver and gut CYPs are also found in extrahepatic sites such as the intestine for CYP3A4 and brain for CYP2D6 Pharmacokinetic investigations in the elderly population reveal decreased clearance of lipophilic drugs metabolized by the cytochrome P450 enzymes only few studies have evaluated agingdependent or genderrelated changes in specific cytochrome P450 enzymes The clearance of quinidine midazolam triazolam erythromycin and lidocaine declines with age these drugs are metabolized by the isoform CYP3A Erythromycin Ndemethylation varied 5fold in human liver microsomes CYP3A activity did not correlate with age smoking status ethanol consumption or percent ideal body weight CYP3A activity was unaffected by age over the range of 2783 years showing that the agingrelated alteration in the clearance of CYP3A substrates is secondary to changes in liver blood flow size or drug binding and distribution with agingDrug clearance appears to be reduced in parallel with reduced liver volume in healthy ageing in man Induction and inhibition in response to age need reexamining because of the increased number of
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