Table 2.
Arithmetic Mean (SD) Plasma and Urine Pharmacokinetic Parameters of Rivaroxaban with and without the Concomitant Administration of Erythromycin in Participants with Normal and Impaired Renal Function
| Rivaroxaban 10 mg | |||
|---|---|---|---|
| PK parameters | Normal renal function (n = 8) | Mild renal impairment (n = 12) | Moderate renal impairment (n = 9) |
| Cmax, ng/mL | 183 (44.6) | 210 (65.4) | 245 (96.6) |
| tmax, ha | 4.00 (2.00–8.00) | 3.00 (1.00–8.00) | 3.00 (1.00–4.00) |
| AUC∞, ng · h/mL | 1798 (459) | 2021 (835) | 2335 (738) |
| t½, h | 7.9 (2.5) | 9.9 (2.4) | 8.9 (1.7) |
| Vd/F, L | 67.7 (32.1) | 77.3 (26.9) | 58.5 (18.6) |
| CL/F, L/h | 5.91 (1.58) | 5.53 (1.74) | 4.68 (1.49) |
| Ae, mg | 3.51 (0.773) | 2.49 (0.697)a | 1.30 (0.654) |
| CLR, L/h | 2.12 (0.833) | 1.40 (0.517)a | 0.594 (0.278) |
| CLGFR, mL/min | 7.39 (2.51) | 6.40 (3.97) | 3.1 (1.15) |
| CLact, mL/min | 27.9 (13.8) | 16.8 (8.91)a | 6.80 (4.43) |
| Rivaroxaban 10 mg + erythromycin 500 mg tid | |||
|---|---|---|---|
| Normal renal function (n = 8) | Mild renal impairment (n = 8) | Moderate renal impairment (n = 8) | |
| Cmax, ng/mL | 256 (62.3) | 287 (77.3) | 323 (172) |
| tmax, ha | 2.50 (1.00–6.00) | 3.00 (1.00–4.00) | 3.00 (1.00–7.98) |
| AUC∞, ng · h/mL | 2,473 (468) | 3,228 (1194) | 3,584 (1005)b |
| t½, h | 7.4 (1.8) | 9.7 (2.7) | 9.8 (2.1)b |
| Vd/F, L | 44.2 (10.4) | 46 (14.7) | 40.9 (9.57)b |
| CL/F, L/h | 4.18 (0.804) | 3.38 (0.931) | 2.96 (0.75)b |
| Ae, mg | 4.80 (0.851) | 3.29 (0.893) | 2.74 (1.10) |
| CLR, L/h | 2.06 (0.650) | 1.15 (0.391) | 0.800 (0.383) |
| CLGFR, mL/min | 7.39 (2.51) | 6.40 (3.97)c | 3.10 (1.15)d |
| CLact, mL/min | 27.0 (11.6) | 12.2 (7.74) | 10.1 (7.01) |
| Rivaroxaban 5 mg + erythromycin 500 mg tid | |||
|---|---|---|---|
| Mild renal impairment (n = 10) | Moderate renal impairment (n = 9) | ||
| Cmax, ng/mL | – | 179 (54.5) | 164 (51.8) |
| DNCmax, ng/mL | – | 358 (109) | 329 (104) |
| tmax, ha | – | 3.00 (1.00–4.00) | 2.00 (1.00–4.00) |
| AUC∞, ng · h/mL | – | 1,967 (835) | 1,981 (510) |
| DNAUC∞, ng · h/mL | – | 3,935 (1,671) | 3,961 (1,020) |
| t½, h | – | 9.6 (3.3) | 10.0 (1.8) |
| Vd/F, L | – | 37.5 (11.7) | 38.1 (11) |
| CL/F, L/h | – | 2.89 (1.05) | 2.68 (0.739) |
| Ae, mg | – | 1.56 (0.692) | 1.04 (0.531) |
| CLR, L/h | – | 0.956 (0.475) | 0.555 (0.272) |
| CLGFR, mL/min | – | 6.40 (3.97)c | 3.10 (1.15) |
| CLact, mL/min | – | 9.39 (9.01) | 6.15 (4.41) |
Data presented as arithmetic mean (SD) unless otherwise noted. Ae, cumulative amount excreted into the urine over 48 hours; AUC∞, area under the plasma concentration–time curve from time 0 to infinity; CLact, active renal clearance; CL/F, total apparent oral clearance of drug; CLGFR, clearance by glomerular filtration; CLR, renal clearance; Cmax, maximum plasma concentration; DN, dose-normalized; h, hour; PK, pharmacokinetics; SD, standard deviation; t1/2, elimination half-life; tid, three times daily; tmax, time to reach the maximum plasma concentration; Vd/F, apparent volume of distribution.
Data presented as median (minimum–maximum).
n = 11.
n = 7.
n = 12.
n = 9.