TABLE 2.
Single-dose PK parameters of atorvastatin, orthohydroxy atorvastatin, and parahydroxy atorvastatin after administration of atorvastatin 40 mg alone and coadministration of atorvastatin 10 mg and steady-state TPV/r 500 mg/200 mg twice daily (n = 22)a
| Analyte and PK parameter | Atorvastatin 40 mg alone (day 1) GM (% CV) | Atorvastatin 10 mg + TPV/r (day 20) GM (% CV)b
|
GM ratio (90% CI)c | P valued | |
|---|---|---|---|---|---|
| Observed | Normalized | ||||
| Atorvastatin | |||||
| AUC0-∞ (h·ng/ml) | 89.3 (38) | 209 (41) | 836 (41) | 9.36 (8.02-10.94) | <0.001 |
| Cmax (ng/ml) | 17.6 (40) | 37.8 (42) | 151 (42) | 8.61 (7.25-10.21) | <0.001 |
| Tmax (h) | 0.5 (0.5-8.0) | 3.0 (1.5-4.0) | 0.001 | ||
| CL/F (liters/h) | 448 (38) | 47.8 (41) | <0.001 | ||
| V/F (liters) | 4536 (43) | 432 (54) | <0.001 | ||
| t1/2 (h) | 7.0 (32) | 6.3 (36) | 0.30 | ||
| Orthohydroxy atorvastatin | |||||
| AUC0-∞ (h·ng/ml) | 117 (21) | 13.6 (124) | 0.11 (0.08-0.17) | 0.002 | |
| Cmax (ng/ml) | 12.4 (41) | 0.301 (35) | 0.02 (0.02-0.03) | <0.001 | |
| Tmax (h) | 1.5 (0.5-8.0) | 4.0 (1.0-12.0) | 0.006 | ||
| t1/2 (h) | 8.6 (21) | 27.7 (158) | 0.010 | ||
| Parahydroxy atorvastatin | |||||
| AUC0-∞ (h·ng/ml) | 19.5 (65) | 4.07 (35) | 0.18 (0.14-0.24) | 0.001 | |
| Cmax (ng/ml) | 0.586 (54) | 0.610 (32) | 1.04 (0.87-1.25) | 0.795 | |
| Tmax (h) | 9.0 (0.5-24.0) | 4.0 (2.0-5.0) | 0.002 | ||
| t1/2 (h) | 21.0 (99) | 3.17 (41) | 0.001 | ||
| Total HMG-CoA reductase inhibitory activity | |||||
| AUC0-∞ (h·nM) | 393 (27) | 396 (43) | 1,519 (42) | 3.87 (3.13-4.33) | <0.001 |
| Cmax (nM) | 54.8 (37) | 69.4 (42) | 272.6 (42) | 4.97 (3.71-5.51) | <0.001 |
a
Tmax values presented as median (range).
b
Dose adjusted assuming linear PK for atorvastatin (normalized value = observed value × 4).
c
Calculated as the ratio of atorvastatin plus TPV/r to atorvastatin alone.
d
P value for difference between atorvastatin alone and atorvastatin plus TPV/r determined by using the Wilcoxon matched-pairs signed-rank test.