Table III.
Dasatinib Pharmacokinetics in Ten Healthy Volunteers Following a 100 mg Oral Dose Given with and Without Gastric pH Modulators
| Parameter | DAS alone (treatment A) | DAS + RAB (treatment B) | DAS + RAB + BHCl (treatment C) | Geometric mean ratios (90% CI) | ||
|---|---|---|---|---|---|---|
| B to A | C to B | C to A | ||||
| Cmax (ng/mL) | 115 ± 68 | 6.87 ± 3.57***;††† | 103 ± 58 | 0.0757 (0.0342–0.168) | 14.0 (7.7–25.4) | 1.05 (0.48–2.30) |
| AUC0-22 (ng/mL*h) | 395 ± 196 | 57.9 ± 28.7***;††† | 379 ± 161 | 0.165 (0.090–0.303) | 6.66 (4.23–10.5) | 1.10 (0.623–1.92) |
| AUC0−∞ (ng/mL*h)a | 405 ± 200 | 70.5 ± 24.8***;††† | 469 ± 233 | 0.217 (0.113–0.417) | 5.57 (3.81–8.14) | 1.21 (0.671–2.17) |
| Tmax (h) | 1.0 (1.0–4.0) | 2.0 (1.5–12) | 2.0 (0.50–4.0) | N/A | N/A | N/A |
| CL/F (mL/min/kg) | 107 ± 114 | 376 ± 127***;††† | 67.8 ± 42.0 | 4.62 (2.41–8.85) | 0.180 (0.123–0.264) | 0.835 (0.470–1.48) |
| t1/2 (h) | 4.43 ± 0.64 | 11.2 ± 7.2***;†† | 5.29 ± 1.04 | 2.10 (1.42–3.11) | 0.553 (0.391–0.781) | 1.16 (1.03–1.31) |
DAS dasatinib, RAB rabeprazole, BHCl betaine HCl, C max maximum plasma concentration, T max time to maximum plasma concentration, t 1/2 terminal half-life, AUC area under the plasma concentration-time curve, CL/F oral clearance, N/A not available
Statistical results for treatment B versus A comparisons and Treatment C versus B comparisons are reported in each row of the Treatment B column. No significant differences were observed for all pharmacokinetic parameters in treatment C versus A comparisons, and in Tmax across all treatments
**P < 0.01; ***P < 0.001; ††P < 0.01; †††P < 0.001
aData from one subject was excluded from analysis as the terminal phase of dasatinib pharmacokinetics could not be estimated