Evaluation of Drug–Drug Interactions Between Clarithromycin and Direct Oral Anticoagulants Using Physiologically Based Pharmacokinetic Models

Figures

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  Figure 1. Individually observed (dots) and population-simulated (lines) plasma concentration–time profiles for clarithromycin: a single 30 min IV infusion of clarithromycin at a dose of 250 mg (a), a single oral administration of clarithromycin at a dose of 250 mg (b), a single oral administration of clarithromycin at a dose of 500 mg (c), clarithromycin administered orally multiple times at a dose of 250 mg, BID (d), clarithromycin administered orally multiple times at a dose of 500 mg, BID (e).

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  Figure 2. Individually observed (dots) and population-simulated (lines) plasma concentration–time profiles for rivaroxaban: a single 30 min IV infusion of dabigatran at a dose of 1 mg (a), a single oral administration of DABE at a dose of 150 mg (b), a single oral administration of DABE at a dose of 300 mg (c), a single 30 min IV infusion administration of rivaroxaban at a dose of 1 mg (d), a single oral administration of rivaroxaban at a dose of 5 mg (e), a single oral administration of rivaroxaban at a dose of 10 mg (f), a single 20 mg oral dose of rivaroxaban administered in a fasted state (g) and a fed state (h), a single 30 min IV infusion administration of apixaban at a dose of 2.5 mg (i), a single oral administration of apixaban at a dose of 10 mg (j), a single oral administration of apixaban at a dose of 20 mg (k), a single 30 min IV infusion administration of edoxaban at a dose of 30 mg (l), a single oral administration of edoxaban at a dose of 60 mg (m), a single oral administration of edoxaban at a dose of 90 mg (n).

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  Figure 3. P-gp parameter sensitivity analysis. Presented are P-gp scaling factor vs predicted AUC0-inf for (a) DAB, (b) rivaroxaban, (c) apixaban, and (d) edoxaban (baseline = 1).

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  Figure 4. Individually observed (dots) and population-simulated (lines) plasma concentration–time profiles: plasma concentration–time curve of dabigatran (a), plasma concentration–time curve of rivaroxaban (b), plasma concentration–time curve of apixaban (c), plasma concentration–time curve of edoxaban (d). Lines represent mean, and error bars represent 90% confidence intervals.