Table 2.
Summary pharmacokinetic parameters of darapladib and its three metabolites following 10 day, once daily dosing of 160 mg of enteric-coated, micronized, free-base darapladib in severely renally impaired subjects and matched healthy control subjects
| Geometric LS Mean (CV%) | |||||
|---|---|---|---|---|---|
| Parameter (units) | Test | Reference | Ratio* | 90% CI | % CVb |
| Total darapladib | |||||
| AUC(0,τ) (ng ml–1 h) | 704.6 (48.9) | 465.1 (27.3) | 1.52 | (1.09, 2.11) | 39.3 |
| Cmax (ng ml–1) | 42.4 (55.6) | 26.7 (43.7) | 1.59 | (1.05, 2.40) | 49.8 |
| tmax (h) | 8 (6–10) | 7 (0–8) | 2 | (0, 6) | NE |
| M3 | |||||
| AUC(0,t) (ng ml–1 h) | 42.9 (141.4) | 18.8 (60.8) | 2.28 | (1.09, 4.79) | 101.3 |
| Cmax (ng ml–1) | 3.7 (168.7) | 2.1 (57.7) | 1.76 | (0.80, 3.91) | 112.4 |
| tmax (h) | 8 (4–10) | 6 (6–10) | 2 | (0, 2) | NE |
| M4 | |||||
| AUC(0,t) (ng ml–1 h) | 28.5 (94.7) | 14.6 (51.9%) | 1.95 | (1.09, 3.50) | 74.3 |
| Cmax (ng ml–1) | 2.4 (150.8) | 1.6 (71.1) | 1.52 | (0.69, 3.33) | 110.5 |
| tmax (h) | 8 (4–10) | 6 (6–10) | 0 | (–2, 2) | NE |
| M10 | |||||
| AUC(0,t) (ng ml–1 h) | 15.2 (52.9) | 7.5 (27.4) | 2.01 | (1.42, 2.86) | 41.6 |
| Cmax (ng ml–1) | 0.76 (52.7) | 0.51 (100.5) | 1.49 | (0.82, 2.73) | 77.7 |
| tmax (h) | 10 (3–24) | 10 (2–24) | 0 | (–7, 8) | NE |
| Unbound darapladib | |||||
| AUC(0,τ) (ng ml–1 h) | 0.33 (64.2) | 0.16 (65.3) | 2.13 | (1.26, 3.59) | 64.8 |
| Cmax (ng ml–1) | 0.02 (71.0) | 0.0090 (86.8) | 2.23 | (1.21, 4.11) | 79.0 |
| tmax (h) | 8 (6–10) | 7 (0–8) | 2 | (0, 6) | NE |
*
Estimated median difference presented for tmax.
CV, coefficient of variation; NE, not estimated.