CYP2D6 Metabolism in Frail Elderly Compared to Non-Frail Elderly: A Pilot Feasibility Study

Frailty is a clinical phenotype that is associated with adverse health outcomes. Since frail patients may be more prone for adverse drug events and about 15-20 % of commonly prescribed drugs are metabolized by CYP2D6, we hypothesized that CYP2D6 metabolism is decreased in frail patients compared with healthy subjects.

The (13)C-dextromethorphan breath test (DM-BT) was used to determine CYP2D6 phenotype using (13)C-dextromethorphan ((13)C-DM) as a probe. Eleven frail and 22 non-frail (according to the Fried criteria) subjects aged 70-85 years were phenotyped for CYP2D6.

Despite inequalities in CYP2D6 genotype between frail and non-frail subjects, the CYP2D6 gene activity score was equally distributed between the two groups (1.33 ± 0.50 vs. 1.28 ± 0.752). In male patients, no difference in total and free serum testosterone levels was observed between frail and non-frail men. Serum dehydroepiandrostenedione sulfate (DHEAS) levels were lower in frail subjects (1.56 μmol/L) compared with non-frail subjects (2.36 μmol/L), but the difference was not significant (p = 0.15). Body mass index was significantly correlated to CYP2D6 phenotype, whereas frailty score and individual parameters of frailty, Karnofsky score, and activities of daily living score were not significantly correlated to CYP2D6 phenotype. Although there was no difference in CYP2D6 phenotype observed between frail mean ± standard deviation (mean ± SD) area under the curve for delta over baseline values (0-2 h) (AUCDOB2h) 319 ± 169 ‰ min] and non-frail subjects (mean ± SD AUCDOB2h 298 ± 159 ‰ min), the present sample size is considered too small to draw any firm conclusions regarding a potential phenoconversion of CYP2D6 in frail elderly as compared with healthy subjects.

Frail and non-frail subjects did not differ in CYP2D6 phenotype, taking into account that the precalculated sample size was not achieved. Further studies with more patients are needed in order to adequately understand a possible correlation.