Table 2.
Plasma pharmacokinetic parameters of olaparib (OLA) after the oral administration of a single dose of olaparib (100 mg/kg b.w.) to the IIIOLA group and metformin + olaparib (100 mg/kg b.w. + 100 mg/kg b.w.) to the IMET+OLA group
| Pharmacokinetic parameters | IIIOLA (n = 8) | IMET+OLA (n = 8) | p value IMET+OLA vs. IIIOLA | Gmean ratio*** (90% CI) IMET+OLA vs. IIIOLA |
|---|---|---|---|---|
| Cmax (ng/ml) | 8716.73 ± 6798.10 (78.0) | 9416.94 ± 6330.79 (67.2) | 0.8342* | 1.22 (0.50; 2.99) |
| AUC0-t (ng × h/ml) | 28,276.56 ± 28,159.91 (99.6) | 28,253.68 ± 21,387.83 (75.7) | 0.7527** | 1.38 (0.49; 3.83) |
| AUC0-∞ (ng × h/ml) | 28,575.50 ± 28,313.46 (99.1) | 29,016.69 ± 21,601.76 (74.4) | 0.7527** | 1.41 (0.51; 3.90) |
| tmax (h) | 1.18 ± 0.91 (77.8) | 1.11 ± 0.75 (67.7) | 0.7087** | 0.94 (0.43; 2.07) |
| ka (h−1) | 0.92 ± 0.29 (32.1) | 1.23 ± 0.15 (41.6) | 0.1509* | 1.28 (0.88; 1.87) |
| kel (h−1) | 0.44 ± 0.34 (77.5) | 0.34 ± 0.22 (65.6) | 0.4784* | 0.97 (0.41; 2.31) |
| t0.5 (h) | 4.79 ± 6.06 (126.5) | 3.18 ± 2.28 (71.7) | 0.7527** | 0.97 (0.41; 2.31) |
| Cl/F (l/h) | 7.84 ± 15.21 (193.9) | 2.62 ± 2.07 (79.0) | 0.8336** | 0.73 (0.26; 2.03) |
| Vd/F (l) | 22.49 ± 24.81 (110.3) | 12.51 ± 11.61 (92.8) | 0.5995** | 0.76 (0.22; 2.62) |
Arithmetic means and standard deviations (SD) are shown with coefficients of variation CV (%) in brackets
Cmax the maximum plasma concentration; AUC0-t area under the plasma concentration–time curve from zero to the time of the last measurable concentration; AUC0-∞ area under the plasma concentration–time curve from zero to infinity; tmax – time to the first occurrence of Cmax; ka absorption rate constant; kel elimination rate constant; t0.5 half-life in the elimination phase; Cl/F apparent plasma drug clearance, Vd/F apparent volume of distribution
*t test for equal variance
**Kruskal–Wallis for no normality
***Geometric mean (Gmean) ratio between the IMET+OLA and IIIOLA groups (%) with a 90% confidence interval (CI) in the brackets