Population pharmacokinetics of apixaban in a real‐life hospitalized population from the OptimAT study

Figures

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  FIGURE 1. Prediction‐corrected visual predictive checks. Dots represent the prediction‐corrected observations and black lines link the corresponding medians and 5th and 95th percentiles. The shaded areas are the 90% confidence intervals around the model‐based prediction‐corrected median and 5th and 95th percentiles.

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  FIGURE 2. Model‐based simulated steady‐state apixaban minimal concentration (C min) with variability after intake of 2.5, 5, and 10 mg b.i.d. as a function of chronic kidney disease stage and P‐gp activity (poor metabolizer, light blue; normal metabolizer, light red; and ultra‐rapid metabolizer, green). The gray surface represents the 5th and 95th percentiles of reported C min in patients with atrial fibrillation for each apixaban dosage (34–162 ng/mL for 2.5 mg b.i.d.; 41–230 ng/mL for 5 mg b.i.d.; 41–335 and in patients with deep vein thrombosis and pulmonary embolism (DVT/PE) for 10 mg b.i.d.); the black line represents the limit associated with a 20% increased bleeding risk (C min = 230 ng/mL). 33 Slightly different 5th and 95th percentiles (not presented) have been reported in different indications: 11–90 ng/mL for 2.5 mg b.i.d. in the prevention of DVT/PE after 6 months of therapeutic treatment; 23–109 ng/mL for 2.5 mg b.i.d. in the prevention in elective orthopedic surgery; 22–177 ng/mL for 5 mg b.i.d. in DVT/PE treatment. 32

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  FIGURE 3. Median (black line) and 90% prediction interval (blue shaded surface) simulated concentration–time profiles at steady‐state (5 mg b.i.d.) after the last drug intake (time 0) in (a) P‐gp normal metabolizer and patients with stage 1 chronic kidney disease (CKD) and in (b) P‐gp poor metabolizer and patients with stage 4 CKD. The red line represents the 50 ng/mL target concentration for most of the extracranial procedures.