Table 2.
Population estimates of pharmacokinetic parameters for AR‐H067637
| Parameter | Estimate (% RSE)* | Inter‐individual variability % (% RSE) |
|---|---|---|
| CL/F (l h−1) ‡ | 39.2 (2.6) | 31 (7.8)† |
| V/F (l) ‡ | 77.8 (10) | 26 (52)† |
| ka (1 h−1) ‡ | 0.0308 (6.3) | 52 (17) |
| Duration (h) ‡ | 1.4 (4.7) | 52 (20) |
| Covariate effects | ||
| Dose on Frel § | −0.42 (7.3) | ‐ |
| Dose 200 mg twice daily on Frel (%) § | −27.9 (9.1) | ‐ |
| eGFR on CL/F (% per ml min−1) ¶ | 0.45 (21) | ‐ |
| Age on CL/F (% per year) ¶ | −0.94 (20) | ‐ |
| Residual error | ||
| Additive (µmol l−1) | 0.0777 (6.8) | ‐ |
| Proportional (%) | 17.2 (6.3) | ‐ |
CL/F, oral clearance; Duration, duration of zero order formation process; eGFR, estimated glomerular filtration rate calculated using the MDRD equation [17]; k a, first order rate constant of the formation process; V/F, oral volume of distribution.
RSE = relative standard error;
Covariance between CL/F and V/F was 26 (RSE 52);
Shrinkage of η was 6.8% for CL/F, 8.6% for V/F, 30% for k a, and 66% for duration;
Relative bioavailability compared with 150 mg AZD0837 once daily, F rel = (dose/150)‐0.42 excluding 200 mg twice daily. F rel 200 mg was 28% lower compared with 150 mg;
Covariate effects of age and renal function on CL/F, relative to the median eGFR of 70 ml min−1 and the median age of 71 years: CL/F = θCL/F × (1 + θeGFR × (eGFR – 65)) × (1 + θAge × (Age – 71)).