Table 3.
Pharmacokinetic parameters of paclitaxel after oral administration of Genetaxyl given in combination with oral cyclosporin A (10 mg/kg)a
| Parameter | 60 mg/m2 (n=6) | 120 mg/m2 (n=6) | 180 mg/m2 (n=6) |
|---|---|---|---|
| Absolute dose (mg) | 108 (98–117) | 198 (180–222) | 296 (270–320) |
| Tmax (h) | 1.50 (1.05–2.00) | 2.50 (1.25–3.00) | 2.01 (1.00–4.00) |
| Cmax (µg/mL) | 0.185 (0.147–0.350) | 0.206 (0.129–0.424) | 0.290 (0.222–0.529) |
| AUCt (µg×h/mL) | 1.29 (1.12–1.64) | 1.60 (1.03–2.41) | 1.85 (0.865–9.51) |
| %CV | 14.5 | 37.8 | 63.9 |
| AUCu/AUCt (%) | 14.2 (9.95–21.9) | 12.5 (10.0–20.1) | 8.61 (7.42–10.1) |
| Bioavailability (%) | |||
| Unbound | 39.5 (16.1–67.5) | 27.6 (17.6–51.7) | 25.9 (16.7–76.9) |
| Total | 42.2 (22.3–56.0) | 29.8 (14.9–42.3) | 30.1 (29.8–65.5) |
| T1/2 (h) | 19.7 (14.5–23.2) | 17.9 (14.3–21.6) | 20.8 (14.4–24.9) |
Abbreviations: n, number of patients; Cmax, peak plasma concentration; AUC, area under the plasma concentration versus time curve extrapolated to infinity; u, unbound paclitaxel; t, total paclitaxel; %CV, percent coefficient of variation in AUCt; CL, systemic clearance; T1/2, half-life of the terminal phase.
a
All data are shown as median value for total paclitaxel, unless indicated otherwise, with range in parenthesis.