Peak plasma concentration of direct oral anticoagulants in obese patients weighing over 120 kilograms: A retrospective study

Abstract

Background: Due to a paucity of data on the efficacy and safety of direct oral anticoagulants (DOACs) in patients with a body mass index >40 kg/m2 or a weight >120 kg, the use of DOACs in this group is not recommended. Objectives: To determine the proportion of obese patients with body weight >120 kg with a peak plasma concentration of DOACs lower than the expected median trough level derived from population pharmacokinetic studies for each DOAC. Methods: Patients with body weight >120 kg taking DOACs for any indication underwent a peak drug concentration measurement at steady state. Results: 38 patients were included in the analysis. The mean age was 64 ± 11 years, and 30 (79%) were males. The median body weight was 132.5 kg (interquartile range [IQR] 127-146.5). The median peak concentrations (IQR) were 148 ng/mL (138-240), 138 ng/mL (123-156.5), 215 ng/mL (181-249) for apixaban, dabigatran, and rivaroxaban, respectively. Two patients (5%, 95% confidence interval [CI]: 0.5%-18%) had a peak plasma concentration lower than the median trough and eight (21%, 95% CI: 11%-37%) had a peak plasma concentration below the fifth percentile (10th percentile for dabigatran) peak concentration. Conclusions: Most patients in our study had peak plasma concentration higher than the median trough level for each of the three DOACs. However, 21% had a peak plasma concentration that was below the usual on-therapy range of peak concentration for the corresponding DOAC.