Pharmacokinetic parameters of pioglitazone and its M-III and M-IV metabolites after administration of pioglitazone 15 mg alone or 1 hour after abiraterone acetate (AA)
| Parameters | Pioglitazone Alone (n = 16) | Pioglitazone + AA (n = 15) | GMR (90% CI) (n = 15) |
|---|---|---|---|
| Pioglitazone | |||
| Cmax (ng/ml) | 338 (120) | 415 (124) | 125 (99.9–156) |
| tmax (h)a | 3.0 (0.5–4.0) | 4.0 (0.5–4.0) | — |
| AUClast (h ⋅ ng/ml) | 4440 (1220) | 6330 (1330) | 146 (126–171) |
| AUC∞ (h ⋅ ng/ml) | 4490 (1220) | 6380 (1330) | 146 (126–169) |
| CL/F (liters/h) | 3.55 (0.866) | 2.46 (0.599) | — |
| t1/2 (h) | 9.30 (2.52) | 8.56 (2.30) | — |
| M-III | |||
| Cmax (ng/ml) | 72.5 (23.6) | 61.7 (16.4) | 86.6 (70.8–106) |
| tmax (h)a | 12.0 (6.0–36.0) | 24.0 (12.0–36.0) | — |
| AUClast (h · ng/ml) | 3110 (1090) | 2710 (714) | 89.9 (77.5–104) |
| AUC∞ (h ⋅ ng/ml) | 3560 (1420)b | 3110 (821)c | 100 (85.8–117)e |
| t1/2 (h) | 20.6 (3.00)b | 21.8 (3.11)c | — |
| M/P Cmax ratio | 0.21 (0.03) | 0.15 (0.03) | — |
| M/P AUClast ratio | 0.67 (0.12) | 0.41 (0.09) | — |
| M/P AUC∞ ratio | 0.75 (0.14)b | 0.48 (0.10)c | — |
| M-IV | |||
| Cmax (ng/ml) | 168 (62.8) | 145 (36.7) | 88.14 (74.7–104) |
| tmax (h)a | 12.0 (8.0–24.0) | 24.0 (12.0–36.0) | — |
| AUClast (h · ng/ml) | 7580 (2321) | 6720 (1450) | 90.5 (79.8–103) |
| AUC∞ (h · ng/ml) | 8380 (2410)d | 7620 (2030)c | 91.5 (82.0–102)e |
| t1/2 (h) | 20.7 (4.10)d | 19.6 (2.68)c | — |
| M/P Cmax ratio | 0.48 (0.09) | 0.34 (0.05) | — |
| M/P AUClast ratio | 1.67 (0.42) | 1.03 (0.16) | — |
| M/P AUC∞ ratio | 1.97 (0.49)d | 1.20 (0.25)c | — |
AUC, area under the curve; CI, confidence interval; CL/F, apparent total clearance of the drug from plasma after oral administration; GMR, geometric mean ratio; M/P, metabolite-to-parent ratio after correction for the difference in their molecular weight.
↵a All pharmacokinetic parameters are reported as the mean (S.D.) except for tmax, for which the median (range) is reported.
↵b For AUC∞, n = 13 due to one subject having a negative slope (lambda z not assessable) and two subjects having unacceptably high variability in the terminal phase.
↵c For AUC∞, n = 9 due to one subject having a negative slope (lambda z not assessable) and five subjects having unacceptably high variability in the terminal phase.
↵d For AUC∞, n = 11 due to five subjects having unacceptably high variability in the terminal phase.
↵e For geometric mean ratio of M-III and M-IV AUC∞, n = 8.