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Association between inherited CYP2D6/2C19 phenotypes and anticholinergic measures in elderly patients using anticholinergic drugs


Kersten, Hege, Wyller, Torgeir B., Molden, Espen


Therapeutic Drug Monitoring, Volume: 36, No.: 1, Pages.: 125-130

Year of Publication



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.;

Bibtex Citation

@article{Kersten_2013, doi = {10.1097/ftd.0b013e31829da990}, url = {}, year = 2013, month = {oct}, publisher = {Ovid Technologies (Wolters Kluwer Health)}, pages = {1}, author = {Hege Kersten and Torgeir B. Wyller and Espen Molden}, title = {Association Between Inherited {CYP}2D6/2C19 Phenotypes and Anticholinergic Measures in Elderly Patients Using Anticholinergic Drugs}, journal = {Therapeutic Drug Monitoring} }


adverse effects, age factors, aged, 80 and over, anticholinergic, aryl hydrocarbon hydroxylases, chemically induced, cholinergic antagonists, cognition, drug effects, drugs, female, genetics, humans, male, mutation, norway, nursing homes, of, pharmacogenetics, pharmacokinetics, pharmacology, phenotype, radioligand assay, statistics nonparametric, users, xerostomia

Countries of Study


Types of Dementia

Mild Cognitive Impairment (MCI)

Types of Study

Cohort Study

Type of Interventions

Risk Factor Modification