Table 3.
Effect of Patiromer on Pharmacokinetic Parameters of Each Victim Drug.a
| PK Parameter | n | Victim Drug Alone | n | Victim Drug Administered Together With Patiromerb | n | Patiromer Administered 3 Hours After Victim Drugc |
|---|---|---|---|---|---|---|
| Amlodipine, 10 mg | 14 | 13 | 14 | |||
| AUC0-∞, h·ng/mL | 315.7 (34.2) | 253.5 (25.2) | 308.0 (32.4) | |||
| C max, ng/mL | 5.74 (24.6) | 4.78 (20.9) | 5.73 (22.9) | |||
| t max, hours | 9.01 (55.2) | 9.31 (45.0) | 6.29 (35.5) | |||
| t 1/2, hours | 39.1 (39.7) | 36.6 (20.0) | 39.5 (33.6) | |||
| Cinacalcet, 90 mg | 43 | 42 | 40 | |||
| AUC0-∞, h·ng/mL | 528 647 (49.0) | 463 671 (55.6) | 504 614 (47.7) | |||
| C max, ng/mL | 45 788.7 (50.5) | 41 265.4 (61.8) | 46 227.6 (51.5) | |||
| t max, hours | 4.04 (23.9) | 4.53 (55.6) | 3.95 (24.1) | |||
| t 1/2, hours | 70.70 (27.0) | 65.42 (27.2) | 70.30 (24.9) | |||
| Ciprofloxacin, 500 mg | 20 | 18d | 20 | |||
| AUC0-∞, h·ng/mL | 7398.9 (25.6) | 5375.8 (24.6) | 7162.3 (27.7) | |||
| C max, ng/mL | 1565.0 (29.2) | 1035.6 (42.3) | 1635.1 (23.3) | |||
| t max, hours | 1.63 (47.5) | 2.90 (55.6) | 1.50 (48.0) | |||
| t 1/2, hours | 5.36 (17.6) | 5.06 (18.0) | 4.93 (19.6) | |||
| Clopidogrel, 75 mg | 50 | 47e | 50 | |||
| AUC0-∞, h·ng/mL | 10.97 (80.2) | 10.80 (110.7) | 10.74 (86.4) | |||
| C max, ng/mL | 3.83 (92.3) | 2.95 (162.6) | 4.09 (136.7) | |||
| t max, hours | 2.08 (38.0) | 2.98 (44.0) | 2.14 (39.4) | |||
| t 1/2, hours | 6.03 (47.1) | 8.56 (54.0) | 5.16 (47.6) | |||
| Furosemide, 40 mg | 39 | 38f | 38f | |||
| AUC0-∞, h·ng/mL | 1460 (29.4) | 1261 (35.6) | 1376 (31.4) | |||
| C max, ng/mL | 449.6 (63.0) | 357.7 (42.1) | 433.1 (55.1) | |||
| t max, hours | 3.11 (34.7) | 2.62 (54.8) | 3.25 (39.2) | |||
| t 1/2, hours | 3.10 (37.0) | 2.97 (32.0) | 2.82 (24.6) | |||
| Levothyroxine, 0.6 mg | 35 | 34 | 34 | |||
| AUC0-48, h·ng/mLg | 1180.6 (20.9) | 980.21 (25.6) | 1158.9 (20.8) | |||
| C max, ng/mL | 47.96 (23.4) | 45.20 (37.4) | 45.93 (20.1) | |||
| t max, hours | 2.189 (82.0) | 2.163 (66.8) | 2.136 (35.1) | |||
| t 1/2, hours | NA | NA | NA | |||
| Lithium, 600 mg | 16 | 16 | 16 | |||
| AUC0-∞, h·ng/mL | 66 719 (20.8) | 68 462 (21.7) | 64 352 (19.6) | |||
| C max, ng/mL | 3728 (14.6) | 3336 (16.9) | 3513 (13.2) | |||
| t max, hours | 2.275 (26.5) | 3.054 (39.4) | 2.264 (28.3) | |||
| t 1/2, hours | 24.27 (15.4) | 24.87 (17.7) | 24.00 (13.5) | |||
| Metformin, 1000 mg | 17 | 17 | 17 | |||
| AUC0-∞, h·ng/mL | 7954 (18.9) | 6706 (33.9) | 7780 (17.6) | |||
| C max, ng/mL | 1185 (18.5) | 808.2 (28.7) | 1173 (16.9) | |||
| t max, hours | 2.680 (25.4) | 3.390 (41.3) | 2.771 (28.4) | |||
| t 1/2, hours | 4.60 (27.1) | 4.71 (36.2) | 4.20 (22.9) | |||
| Metoprolol, 100 mg | 25 | 25 | 25 | |||
| AUC0-∞, h·ng/mL | 1228 (78.1) | 1085 (87.1) | 1159 (80.6) | |||
| C max, ng/mL | 181.9 (47.1) | 142.9 (54.9) | 189.3 (47.3) | |||
| t max, hours | 2.24 (37.7) | 2.87 (46.5) | 2.02 (43.6) | |||
| t 1/2, hours | 4.468 (37.4) | 4.663 (35.2) | 4.261 (41.1) | |||
| Trimethoprim, 200 mg | 18 | 18 | 18 | |||
| AUC0-∞, h·ng/mL | 25 573 (27.3) | 22 259 (24.1) | 22 380 (26.2) | |||
| C max, ng/mL | 1608.12 (24.3) | 1335.58 (22.3) | 1599.48 (22.4) | |||
| t max, hours | 2.75 (16.8) | 3.53 (40.3) | 2.86 (10.1) | |||
| t 1/2, hours | 9.75 (22.9) | 9.51 (18.5) | 8.79 (22.1) | |||
| Verapamil, 120 mg | 63 | 62 | 62 | |||
| AUC0-∞, h·ng/mL | 865.6 (44.3) | 1210 (29.2) | 875.3 (47.5) | |||
| C max, ng/mL | 165.2 (45.3) | 113.1 (35.7) | 168.8 (61.4) | |||
| t max, hours | 1.948 (45.5) | 2.759 (43.2) | 2.182 (39.9) | |||
| t 1/2, hours | 9.981 (19.8) | 9.219 (15.6) | 9.528 (17.9) | |||
| Warfarin-R, 25 mg | 15 | 14 | 15 | |||
| AUC0-∞, h·ng/mL | 95 350 (24.0) | 95 240 (21.4) | 97 090 (23.0) | |||
| C max, ng/mL | 1416 (14.5) | 1395 (18.6) | 1425 (14.3) | |||
| t max, hours | 4.804 (46.7) | 5.115 (57.0) | 4.805 (50.0) | |||
| t 1/2, hours | 51.94 (19.5) | 51.44 (22.0) | 52.64 (20.5) | |||
| Warfarin-S, 25 mg | 15 | 14 | 15 | |||
| AUC0-∞, h·ng/mL | 53 380 (38.2) | 53 030 (40.2) | 54 240 (39.5) | |||
| C max, ng/mL | 1366 (15.6) | 1354 (23.7) | 1387 (18.3) | |||
| t max, hours | 4.069 (47.8) | 3.468 (63.1) | 3.403 (41.5) | |||
| t 1/2, hours | 37.43 (21.5) | 35.05 (16.3) | 37.77 (18.7) |
Abbreviations: AUC0-∞, area under the plasma concentration time curve from time 0 extrapolated to infinity; C max, maximum observed plasma concentration; CV%, coefficient of variation; LCL, lower confidence limit; NA, not assessed; PK, pharmacokinetic; UCL, upper confidence limit; t max, time to maximum concentration; t 1/2, apparent elimination half-life.
aData presented as arithmetic mean (CV%).
bLevothyroxine which is recommended to be administered from 1/2 hour to 1 hour before meal, and patiromer is recommended to be administered with food, so the 2 drugs were not administered at the same time, and “administered together” represents a 40-minute separation between levothyroxine and patiromer.
cThe first patiromer dose was administered 21 hours before victim drug, and the second patiromer dose was administered 3 hours after victim drug.
dCiprofloxacin C max and t max n = 19.
eClopidogrel C max and t max n = 50.
fFurosemide C max and t max n = 39.
gBaseline-adjusted AUC0-48 is used because extrapolation to infinity is not valid for levothyroxine, because thyroid hormone values do not go to 0 due to endogenous production.