Study on Pharmacokinetics and Safety of Etoricoxib Tablets in Chinese Healthy Subjects

OBJECTIVE To study the pharmacokinetics and safety of etoricoxib in Chinese healthy subjects following single oral administration under fasting and fed conditions. METHODS Sixty-eight healthy subjects were randomly divided into a fasting group and a fed group, and administered using a 2-period crossover trial design, LC-MS/MS was used to determine the concentration of etoricoxib in human plasma. The pharmacokinetic parameters were calculated using WinNonLin software, to compare the pharmacokinetic differences between domestic etoricoxib and original reference preparations, and the effects of different genders and meals on the pharmacokinetic parameters of etoricoxib were compared. The safety of etoricoxib tablets was evaluated by vital signs, physical examination, laboratory test results and electrocardiogram changes. RESULTS The pharmacokinetic parameters of the test and reference preparations in the fasting group were as follows:T_max 1.25, 1.25 h, C_max (2 767.50±421.89), (2 707.81±674.90)ng·mL^-1, AUC_0-∞ (52 967.87±13 843.25), (53 479.56±16 066.32)h·ng·mL^-1. The pharmacokinetic parameters of the test and reference preparations in the fed group were as follows:T_max 2.50, 1.75 h, C_max (2 000.61±314.89), (2 209.06±429.05)ng·mL^-1, AUC_0-∞ (51 450.80±17 241.02), (49 287.23±16 192.87)h·ng·mL^-1. There was a statistically significant difference in T_max between the test and reference preparations in the fed group(P<0.05), but it has no clinical significance. After the subjects took oral etoricoxib tablets on an empty stomach and after meals, there was a statistically significant difference in T_max and C_max(P<0.01), but there was no statistically significant difference in AUC_0-∞. There was no significant difference in the main pharmacokinetic parameters T_max, C_max, and AUC_0-∞ among subjects of different genders after oral administration of etoricoxib tablets under fasting condition, but t_1/2 and AUC_0-∞ were higher in female subjects compared with male subjects after postprandial administration(P<0.05). Adverse events after fasting and postprandial administration involve multiple systems and were mild without serious adverse reactions. CONCLUSION Domestic etoricoxib tablets and original reference preparations have bioequivalence; meals affect the absorption rate of etoricoxib tablets, but do not affect the extent of absorption; there are no gender differences in pharmacokinetic parameters of etoricoxib after fasting administration, but there are gender differences in t_1/2, AUC_0-∞ after postprandial administration. Etoricoxib tablets have good safety and tolerance in Chinese healthy subjects.