Table 4.
Parameter estimates in the final population pharmacokinetic model
| Fixed effects parameters | Estimate | SE | Description |
|---|---|---|---|
| ka (1/hr) | 0.440 | 0.0209 | Administration of apixaban in the evening resulted in a 46% decrease relative to administration in the morning or afternoon |
| An evening dose | 0.239 | 0.0126 | |
| CLR/Fa (L/hr) | 1.83 | 0.169 | VTE treatment subjects with mild (cCrCL of 65 mL/min), moderate (cCrCL of 40 mL/min), and severe (cCrCL of 15 mL/min) renal impairment would have approximately 35%, 60%, and 85% lower CLR/F, respectively, than a reference VTE treatment subject with normal renal function (cCrCL of 100 mL/min) |
| CLNR/F (L/hr) | 2.52 | 0.162 | |
| Agea | −0.267 | 0.0503 | For example, a 40‐year‐old and 80‐year‐old male VTE treatment subject would have 11% higher and 7% lower CLNR/F relative to a reference VTE treatment male subject who is 60 years old |
| Female | −0.223 | 0.0331 | Female subjects had 22.3% lower CLNR/F relative to male subjects, resulting in 13% lower CL/F, assuming no change in CLR/F |
| CL/F | |||
| Asian subjects | −0.168 | 0.0374 | Asian race resulted in a decrease of 16.8% in CL/F |
| Strong/moderate CYP3A4/P‐gp Inhibitors | −0.203 | 0.051 | Concomitant use of strong or moderate CYP3A4/P‐gp inhibitors resulted in a decrease of 20.3% in CL/F |
| Vc/F (L) | 32.1 | 1.16 | |
| Body weighta | 0.523 | 0.0694 | The effect of baseline body weight on Vc/F was less than directly proportional, with a 24% reduction for a 50‐kg subject and a 20% increase for a 120‐kg subject relative to the reference subject with a body weight of 85 kg |
| Q/F (L/hr) | 1.62 | 0.125 | |
| Vp/F (L) | 19.8 | 1.3 |
CrCL, creatinine clearance using Cockcroft‐Gault formula; CL/F, apparent total clearance; CLNR/F, apparent non‐renal clearance; CLR/F, apparent renal clearance; Ka, absorption rate constant; Q/F, apparent intercompartmental clearance; SE, standard error; Vc/F, apparent volume of central compartment; Vp/F, apparent volume of peripheral compartment; VTE, venous thromboembolism; CYP3A4, Cytochrome P450 3A4; P‐gp, P‐glycoprotein.
a
aCentered at reference VTE treatment subject values: 60 years, 85 kg with cCrCL = 100 mL/min.