Pharmacokinetic parameters after single oral administrations of P-glycoprotein substrates (fexofenadine, talinolol, and aliskiren) to cynomolgus monkeys with or without curcumin or elacridar pretreatment
Data are expressed as means ± S.E. of cynomolgus monkeys in each group. There were no significant differences, except in Tmax, between UT and curcumin pretreatment as determined by a paired t test.
| Pretreatment Parameter | UT Value | Curcumin 30 mg/kg | Elacridar 5 mg/kg | |||
|---|---|---|---|---|---|---|
| Value | Ratio | Value | Ratio | |||
| FEX 2 mg/kg (N = 7) | AUCall (ng·h/ml) | 229 ± 29 | 210 ± 28 | 1.0 ± 0.2 | 1220 ± 80*** | 5.7 ± 0.6 |
| T1/2 (h) | 8.01 ± 0.85 | 10.1 ± 1.4a | 1.4 ± 0.2a | 4.57 ± 0.77* | 0.60 ± 0.10 | |
| Cmax (ng/ml) | 48.4 ± 6.2 | 58.6 ± 22.2 | 1.3 ± 0.4 | 478 ± 61*** | 11 ± 2 | |
| Tmax (h) | 1.57 ± 0.20 | 1.00 ± 0.19* | 0.68 ± 0.12 | 1.29 ± 0.19 | 0.93 ± 0.20 | |
| TLN 1 mg/kg (N = 4) | AUCall (ng·h/ml) | 32.1 ± 7.7 | 32.8 ± 6.3 | 1.0 ± 0.1 | 48.9 ± 10.0* | 1.6 ± 0.2 |
| T1/2 (h) | 9.08 ± 0.19 | 8.34 ± 0.30 | 0.92 ± 0.04 | 7.30 ± 0.38b | 0.82 ± 0.05b | |
| Cmax (ng/ml) | 9.00 ± 2.20 | 7.67 ± 1.25 | 0.90 ± 0.12 | 15.2 ± 5.3 | 1.6 ± 0.2 | |
| Tmax (h) | 0.875 ± 0.125 | 1.25 ± 0.25 | 1.5 ± 0.3 | 2.00 ± 1.34 | 2.3 ± 1.3 | |
| AL 3 mg/kg (N = 4) | AUCall (ng·h/ml) | 160 ± 34 | 165 ± 39 | 1.1 ± 0.3 | 622 ± 130* | 4.0 ± 0.4 |
| T1/2 (h) | NC | 16.9 ± 5.4 | NC | 12.1 ± 3.1b | NC | |
| Cmax (ng/ml) | 24.5 ± 3.5 | 32.8 ± 21.0 | 1.4 ± 0.9 | 157 ± 40* | 6.4 ± 1.0 | |
| Tmax (h) | 2.19 ± 1.33 | 1.75 ± 0.83 | 4.5 ± 3.8 | 2.63 ± 1.18 | 6.6 ± 5.8 | |