Table 3.
Summary statistics of milvexian plasma and urine PK parameters by renal function group
| Parametera | Normal renal functionb [n = 8] | Moderate renal impairmentc [n = 8] | Severe renal impairmentd [n = 8] |
|---|---|---|---|
| Cmax, ng/mL | 462 (30) | 406 (46) | 462 (42) |
| %fu | 8.85 (8) | 8.81 (11) | 8.40 (15) |
| Cmax fu, ng/mL | 40.9 (29) | 35.8 (44) | 38.8 (44) |
| AUCt, ng·h/mL | 3860 (36) | 5004 (34) | 7094 (33) |
| AUCt fu, ng·h/mL | 341 (33) | 441 (32) | 596 (41) |
| AUC∞, ng·h/mL | 3916 (36) | 5154 (32) | 7411 (37) |
| AUC∞ fu, ng·h/mL | 347 (34) | 454 (30) | 623 (44) |
| AUC96, ng·h/mL | 3883 (36) | 5015 (34) | 7167 (35) |
| Tmax, h | 4.50 (4.00–5.00) | 4.75 (4.00–7.00) | 5.00 (4.50–8.00) |
| T½, h | 13.8 (3.45) | 18.0 (5.37) | 17.7 (4.75) |
| CLT/F, L/h | 15.3 (36) | 11.6 (32) | 8.10 (37) |
| CLT/F fu, L/h | 173 (33) | 132 (30) | 96.4 (44) |
| CLR, mL/h | 1617 (52) | 914 (40) | 263 (65) |
| %Urt | 10.5 (45) | 7.64 (33) | 3.14 (75) |
| %Protein binding | 91.1 (1) | 91.1 (1) | 91.5 (1) |
PK pharmacokinetic, Cmax maximum observed plasma concentration, fu fraction of unbound drug, Cmax fu maximum observed plasma concentration of free drug, AUCt area under the plasma concentration-time curve from time zero to time of the last quantifiable concentration, AUCt fu AUC from time zero to time of the last quantifiable concentration of free drug, AUC∞ AUC from time zero extrapolated to infinite time, AUC∞ fu AUC from time zero extrapolated to infinite time of free drug, AUC96 AUC from time zero to 96 h, Tmax time of maximum observed plasma concentration, T½ terminal plasma half-life, CLT/F apparent total body clearance, CLT/F fu apparent total body clearance of free drug, CLR renal clearance, %Urt percentage dose of milvexian total amount recovered in urine, %CV percentage coefficient of variation, SD standard deviation
aCmax, %fu, Cmax fu, AUCt, AUCt fu, AUC∞, AUC∞ fu, AUC96, CLT/F, CLT/F fu, CLR, %Urt, and %protein binding are presented as adjusted geometric mean (%CV); Tmax is presented as median (minimum–maximum); and T½ is presented as mean (SD)
bNormal renal function was an eGFR ≥ 90 mL/min/1.73 m2
cModerate renal impairment was an eGFR ≥ 30 to ≤59 mL/min/1.73 m2
dSevere renal impairment was an eGFR < 30 mL/min/1.73 m2