国产达沙替尼治疗慢性髓性白血病慢性期患者的药代动力学研究

OBJECTIVE: To evaluate the pharmacokinetics and bioequivalence of generic dasatinib in patients with chronic myeloid leukemia in the choronie phase (CML-CP). METHODS: Using randomized, parallel, overlapping, self-control designed study, a 100 mg dose of the reference or test tablet was given to 12 CML-CP patients who were resistant or intolerant to Imatinib and Nilotinib in a randomized two-way crossover design, and the plasma concentration of the medicine was assayed by HPLC-MS-MS. The main pharmacokinetic parameters and bioequivalence of the two formulations were evaluated. RESULTS: The major pharmacokinetic parameters were as follows: C(max) (209.01±58.69) µg/L and (223.07±79.51) µg/L, T(max) (1.1±0.8) h and (1.1±0.8) h, T(1/2) (5.10±1.34) h and (4.39±0.74) h, AUC(0-τ) (646.65±185.67) h·µg/L and (695.84±273.40) h·µg/L (all P>0.05); AUC(0-∝) (668.11±186.00) h·µg/L and (712.42±278.08) h·µg/L, MRT (5.32 ± 1.70) h and (4.68 ± 1.53) h (all P>0.05). CONCLUSION: The two formulations were bioequivalent.