Background: Frailty makes older adults vulnerable to adverse health outcomes and can modify pharmacokinetics and drug exposure.

Objective: We aimed to explore the relationship between different frailty assessments and trough plasma concentrations of direct oral anticoagulants in older patients.

Methods: The frailty status of adults aged ≥ 70 years receiving regular direct oral anticoagulant medication was assessed by four different instruments: Fried physical phenotype, Rockwood frailty index, Short Physical Performance Battery, and FRAIL scale. The two performance measures "slow gait speed" and "weak grip strength" were used to build a separate score depending on the number of positive criteria (none, one, two). For each participant, a single steady-state direct oral anticoagulant trough plasma concentration was collected, dose-normalized, and its relationship to the various frailty assessments analyzed.

Results: Forty-two participants completed the study, with most using apixaban (n = 22). Dose-normalized apixaban trough concentrations were 2.48-fold higher in frail participants (Fried phenotype) than in robust participants (p = 0.009) and correlated positively with Fried physical phenotype (r(s) = 0.535, p = 0.010) and negatively with Short Physical Performance Battery (r(s) = - 0.434, p = 0.044). Compared with participants who met none of the criteria "slow gait speed" and "weak grip strength", apixaban trough concentrations were approximately 1.9-fold higher in participants who were positive for one (p = 0.018) or two (p = 0.013) of these measures.

Conclusions: In this exploratory study, higher levels of frailty on performance-based frailty assessments were associated with higher apixaban exposure in older adults.

Clinical trial registration: German Clinical Trials Register DRKS00016741; registered 20 February, 2019.