Summary of pharmacokinetic parameters of a P-gp probe substrate, talinolol, following oral dosing of probe drug cassette in cynomolgus monkey, alone or in combination with single oral doses of rifampicin, elacridar, or probenecid
Values depict mean ± S.D. for pharmacokinetic (PK) parameters and (geometric mean ± S.D.) where ratio of treatment to control group was shown. Statistical significance for AUC0–t, Cmax, t1/2, and CLrenal was tested by one-way analysis of variance with Tukey test for multiple group comparison.
| PK Parameters | Control | + Rifampicin | + Elacridara | + Probenecid |
|---|---|---|---|---|
| AUC0–t (ng × h/ml) | 108 ± 49 | 304 ± 65** | 261 ± 23* | 196 ± 97 |
| AUC ratio | — | (3.0 ± 0.9) | (2.4 ± 1.0) | (1.8 ± 0.4) |
| AUC0–inf (ng × h/ml) | 131 ± 44 | 335 ± 46 | 270 ± 22 | 208 ± 94 |
| Cmax (ng/ml) | 31 ± 24 | 133 ± 35** | 105 ± 16* | 45 ± 29 |
| Cmax ratio | — | (5.3 ± 4.2) | (3.1 ± 1.7) | (1.5 ± 1.1) |
| Tmax (h) | 1.1 ± 0.6 | 0.8 ± 0.3 | 0.5 ± 0.2 | 1.1 ± 0.6 |
| t1/2 (h) | 8.8 ± 3.8 | 5.7 ± 1.4 | 5.0 ± 1.8 | 6.6 ± 2.1 |
| % Bioavailabilityb | 9 ± 2 | — | — | — |
| % Unchanged drug in urine in 24 h | 2.2 ± 0.7 | 2.4 ± 0.7 | 1.8 ± 1.3 | 1.1 ± 0.5 |
| CLrenal (ml/min per kilogram) | 2.9 ± 1.2 | 1.3 ± 0.4 | 0.8 ± 0.4 | 1.1 ± 0.5 |
| CLrenal ratio | (2.2 ± 1.0) | (2.8 ± 0.8) | (2.6 ± 0.8) |
↵a n = 3. One animal was excluded for the analysis in this treatment group due to considerable deviation from the remaining three animals.
↵b % Bioavailability is calculated based on plasma exposure following single i.v. administration of 0.2 mg/kg in the same monkeys (data not shown).
↵** P < 0.01; *P < 0.05.
(—), not calculated.