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Association Between Inherited CYP2D6/2C19 Phenotypes and Anticholinergic Measures in Elderly Patients Using Anticholinergic Drugs

Kersten, Hege PhD*,†; Wyller, Torgeir B. PhD*,‡; Molden, Espen PhD§,¶

doi: 10.1097/FTD.0b013e31829da990
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Background: To compare measures of anticholinergic activity between metabolic phenotypes of the polymorphic enzymes cytochrome P450 2D6 (CYP2D6) and CYP2C19 in the elderly patients exposed to anticholinergic agents.

Methods: Long-term nursing home patients (n = 80) with an anticholinergic drug scale (ADS) score ≥3 were recruited from 22 nursing homes in Norway. Based on pharmacogenetic analyses of mutations encoding absent CYP2D6 or CYP2C19 metabolism, patients were divided into subgroups of poor metabolizers (PMs) (n = 8) and extensive metabolizers (n = 72). Serum anticholinergic activity (SAA) was determined by a validated, 96-well format radio receptor assay and adjusted for ADS score. Unadjusted and adjusted SAAs, mouth dryness, and cognitive function (Mini-Mental State Examination and verbal recall tests from Consortium to Establish a Registry for Alzheimer Disease) were compared between the subgroups with Mann–Whitney tests.

Results: The study population was represented by 78% women, 68% had mild to moderate dementia, and mean age was 86 years. More than 80% used more than 1 anticholinergic agent, and their median ADS score was 4. The subpopulation of PMs had significantly higher median SAA than the extensive metabolizers (10.3 versus 4.2 pmol atropine equivalents per milliliter, P = 0.012). This difference remained significant after adjusting for ADS score (P = 0.013). No significant differences in mouth dryness and cognitive function were observed between the subgroups (P > 0.3).

Conclusions: These preliminary findings suggest that elderly CYP2D6/CYP2C19 PMs with a high anticholinergic drug burden are at increased risk of elevated SAA. Whether PMs are also more prone to experience anticholinergic side effects needs to be further studied in larger patient populations.

*Department of Geriatric Medicine, Oslo University Hospital;

Department of Pharmaceutical Services, The Hospital Pharmacies;

Institute of Clinical Medicine, University of Oslo;

§Department of Pharmaceutical Bioscience, School of Pharmacy, University of Oslo; and

Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.

Correspondence: Hege Kersten, PhD, Department of Geriatric medicine, Oslo University Hospital, 0424 Oslo, Norway (e-mail: hege.kersten@sthf.no).

The South-Eastern Norway Regional Health Authority provided PhD grants to H. Kersten, and The Norwegian Directorate of Health provided financial support to the study nurse, Inga Kristin Tolo.

There were no sponsors of this study. The authors have declared no conflicts of interest.

Received January 24, 2013

Accepted May 27, 2013

© 2014 by Lippincott Williams & Wilkins