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The Role of Sex, Age and Genetic Polymorphisms of CYP Enzymes on the Pharmacokinetics of Anticholinergic Drugs
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  • Shanna Trenaman,
  • Susan Bowles,
  • Melissa Andrew,
  • Kerry Goralski
Shanna Trenaman
Dalhousie University
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Susan Bowles
Nova Scotia Health Authority
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Melissa Andrew
Nova Scotia Health Authority
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Kerry Goralski
Dalhousie University
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Abstract

Drugs exhibiting anticholinergic properties are commonly used by older adults even with the associated risk of adverse drug events. Aging, sex and genetic polymorphisms of cytochrome P450 (CYP) enzymes are associated with alterations in pharmacokinetic processes which may increase drug exposure and further increase the risk of adverse drug events. Age-related changes include; pseudocapillarization of liver sinusoidal endothelial cells which limit passage of drugs through the liver, an approximate 3.5% decline in CYP450 content for each decade of life, and a reduction in kidney function reducing drug excretion. Sex-related differences include; women having delayed gastric and colonic emptying, higher gastric pH, reduced catechol-O-methyl transferase activity, reduced glucuronidation, and reduced renal clearance and men having larger stomachs which may allow them to dissolve and absorb medication more completely. The overlay of poor metabolism phenotypes for CYP2D6 and CYP2C19 may further modify anticholinergic drug exposure in a significant proportion of the population. These factors help explain clinical trials that show older adults and specifically women achieve higher plasma concentrations of anticholinergic drugs. Despite this knowledge, age and sex are rarely considered when making decisions about the dosing of anticholinergic medications. As this is relevant to the future use of personalized medicine, the objective of this review is to provide a clinical perspective on age, sex, and CYP genetic polymorphisms and their role in the metabolism and exposure to anticholinergic drugs. Future work needs to account for age, sex and CYP polymorphism so that we may better approach personalized medicine for optimal outcomes.

Peer review status:POSTED

12 Aug 2020Submitted to British Journal of Clinical Pharmacology
13 Aug 2020Assigned to Editor
13 Aug 2020Submission Checks Completed