关键词: 吉非替尼, 健康人, 生物等效性, HPLC-MS/MS

Abstract:

AIM: To evaluate the bioequivalence of two preparations of gefitinib tablets in healthy Chinese subjects. METHODS: This study was a randomized, open-label, double-period, single-center clinical trial after a single-dose oral administration of 250 mg, 56 subjects were divided into groups of fasting bioequivalence study and postprandial bioequivalence study. The blood concentrations of gefitinib tablets in plasma at different time after drug administration were determined by HPLC-MS/MS. The pharmacokinetic parameters were calculated and analyzed statistically with non compartment model method. RESULTS:The main pharmacokinetic parameters of test and reference(27 subjects) of gefitinib tablets administered fasted were as follows: t1/2 were（20.8±8.3）and（21.5±9.7）h, tmax were（5.63±1.82）and（5.30±1.44）h, Cmax were（200±86）and（203±84）ng/mL, AUC0-t were（4 968±2 268）and（4 853±2 073）ng·h/mL, AUC0-∞ were（5 054±2 325），（4 950±2 111）ng·h/mL, the relative bioavailability calculated by AUC0-tand AUC0-∞were 104.4% and 103.9%, respectively; The main pharmacokinetic parameters of test and reference(28 subjects) of gefitinib tablets administered with food were as follows: t1/2 were（21.1±9.9）and（22.0±10.1）h；tmax were（4.46±2.22）and（4.46±1.82）h；Cmax were（299±106）and（304±119）ng/mL；AUC0-t were（6 700±3 142）and（6 594±3 004 ）ng·h/mL；AUC0-∞ were（6 846±3 265），（6 750±3 136）ng·h/mL , the relative bioavailability calculated by AUC0-t and AUC0-∞ were 101.1% and 100.9%, respectively. CONCLUSION: The two gefitinib tablets administered fasted or with food were bioequivalent in healthy Chinese subjects.

Key words: gefitinib, healthy volunteers, bioequivalence, HPLC-MS/MS