Apixaban, a direct factor Xa inhibitor, has predictable pharmacokinetic and pharmacodynamic properties that are consistent across a wide range of patients, including the elderly and those with moderate renal impairment. |
The fast onset of action, low potential for food or drug interactions, and lack of requirement for routine monitoring during clinical use make apixaban a potentially useful option to simplify anticoagulation treatment. |
1 Introduction
2 Chemical and Physicochemical Properties
2.1 Mode of Action
3 Pharmacokinetic Properties
Dose (mg) |
n
| Cmax (ng/mL) GM (CV %) | AUC0–∞ (ng·h/mL), GM (CV %) | AUC0–t (ng·h/mL) GM (CV %) | Tmax (h) Median (min, max) | t1/2 (h) Mean (SD) |
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Single-ascending-dose study
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Oral solution
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0.5 | 6 | 9.1 (20) | 61.9 (16) | 52.7 (23) | 1.5 (1.0, 4.0) | 3.6 (1.1) |
1.0 | 6 | 23.5 (35) | 174.4 (31) | 162.6 (33) | 1.8 (1.0, 3.0) | 4.3 (1.6) |
2.5 | 6 | 52.5 (35) | 437.5 (41) | 421.1 (42) | 1.5 (1.0, 3.0) | 6.8 (2.0) |
Oral tablet
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5 | 6 | 104.7 (25) | 1016.6 (37) | 976.6 (36) | 3.3 (2.5, 4.0) | 15.2 (8.5) |
10 | 6 | 176.3 (42) | 1303.6 (40) | 1266.5 (38) | 3.0 (2.0, 4.0) | 11.1 (5.8) |
25 | 6 | 365.1 (17) | 4010.0 (19) | 3868.9 (22) | 3.0 (2.5, 4.0) | 26.8a (33.7) |
50 | 7 | 685.2 (22) | 7556.5 (25) | 7096.7 (23) | 2.5 (2.0, 4.0) | 19.7 (15.3) |
Food effect study, oral tablet
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10 fasted | 21 | 150.8 (28) | 1789.0 (31) | 1762.2 (32) | 3.0 (1.5, 6.0) | 11.5 (4.3) |
10 fed | 21 | 165.0 (18) | 1867.8 (30) | 1811.5 (30) | 4.0 (1.0, 9.0) | 11.3 (2.9) |
Apixaban dose (mg) and regimen | Cmax (ng/mL), GM (CV %) | Cmina (ng/mL), GM (CV %) | AUCtaub (ng·h/mL), GM (CV %) | Tmax (h), median (min, max) | AI, GM (CV %) | t1/2 (h), mean (SD) |
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Day 1
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2.5 BID (n = 6) | 51.0 (27) | 14.2 (53) | 353.3 (25) | 3.5 (2.0, 12.0) | – | – |
5 BID (n = 6) | 81.9 (18) | 25.3 (20) | 600.6 (20) | 3.5 (3.0, 6.0) | – | – |
10 BID (n = 6) | 226.2 (38) | 72.7 (27) | 1608.3 (30) | 4.0 (2.0, 4.0) | – | – |
25 BID (n = 6) | 425.3 (24) | 129.0 (33) | 3108.6 (25) | 3.5 (2.0, 4.0) | – | – |
10 QD (n = 6) | 178.4 (19) | 14.5 (27) | 1589.6 (20) | 4.0 (3.0, 4.0) | – | – |
25 QD (n = 6) | 310.0 (12) | 36.5 (31) | 2868.1 (7) | 4.0 (2.0, 6.0) | – | – |
Day 7
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2.5 BID (n = 5) | 62.3 (37) | 21.0 (17) | 462.8 (35) | 3.0 (3.0, 9.0) | 1.3 (18) | 8.1 (1.8) |
5 BID (n = 6) | 128.5 (10) | 49.6 (20) | 1051.9 (9) | 4.0 (2.0, 4.0) | 1.8 (22) | 11.7 (3.3) |
10 BID (n = 6) | 329.8 (45) | 103.8 (57) | 2424.9 (47) | 3.0 (2.0, 4.0) | 1.5 (33) | 10.9 (2.9) |
25 BID (n = 6) | 716.6 (21) | 281.1 (38) | 5850.3 (16) | 3.5 (1.0, 4.0) | 1.9 (17) | 15.2 (7.2) |
10 QD (n = 6) | 201.4 (15) | 26.8 (43) | 2015.7 (16) | 3.5 (3.0, 4.0) | 1.3 (23) | 14.9 (7.2) |
25 QD (n = 6) | 428.9 (20) | 55.3 (33) | 4248.3 (19) | 3.0 (2.0, 4.0) | 1.5 (17) | 15.3 (4.3) |
3.1 Absorption, Bioavailability, and Biopharmaceutical Profile
3.2 Protein Binding and Distribution
3.3 Metabolism and Elimination
3.4 Dose Proportionality and Time Dependency
4 Pharmacokinetic Effects of Intrinsic Factors in Special Populations
4.1 Age
4.2 Sex
4.3 Body Weight
4.4 Race
4.5 Renal Impairment
4.6 Hepatic Impairment
4.7 Pediatric Population
5 Drug Interactions
5.1 Effects of Apixaban on the Pharmacokinetics of Other Drugs
5.2 Effects of Other Drugs on the Pharmacokinetics of Apixaban
6 Pharmacodynamic Properties
Apixaban dose and regimen | Cmax (ng/mL) | Cmin (ng/mL) | Anti-FXa activity maximum (IU/mL) | Anti-FXa activity minimum (IU/mL) |
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Median (5th, 95th percentile)
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Prevention of VTE: elective hip or knee replacement surgery
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2.5 mg BID | 77 (41, 146) | 51 (23, 109) | 1.3 (0.67, 2.4) | 0.84 (0.37, 1.8) |
Prevention of stroke and systemic embolism: NVAF
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2.5 mg BIDa | 123 (69, 221) | 79 (34, 162) | 1.8 (1.0, 3.3) | 1.2 (0.51, 2.4) |
5 mg BID | 171 (91, 321) | 103 (41, 230) | 2.6 (1.4, 4.8) | 1.5 (0.61, 3.4) |
Treatment of VTE and prevetion of recurrent VTE
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2.5 mg BID | 67 (30, 153) | 32 (11, 90) | 1.1 (0.47, 2.4) | 0.51 (0.17, 1.4) |
5 mg BID | 132 (59, 302) | 63 (22, 177) | 2.1 (0.93, 4.8) | 1.0 (0.35, 2.8) |
10 mg BID | 251 (111, 572) | 120 (41, 335) | 4.0 (1.8, 9.1) | 1.9 (0.65, 5.3) |