Bioequivalence Study Of Ibuprofen Sustained-release Capsules In Healthy Human

OBJECTIVE: To establish a rapid and sensitive method for the quantitation of Ibuprofen by LC-MS/MS in healthy human plasma.The method was used to determine the concentrations of Ibuprofen in plasma of volunteers after oral administrations of test drug and reference drug, draw relevant pharmacokinetic parameters and bioequivalence evaluation through statistical analysis.DOSING METHODS: Single dosing and multiple dosingboth were two-period crossover studies, 1-week washout period. Single dosing: 22 male subjects were enrolled in this study, subjects fasted overnight for at least 10 hours before dosing, then received a single 0.3g/capsule dose of test or reference drug. Blood samples were collected at pre-dose and at 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 10 h, 12 h, 15 h and 24 hours after dosing for drug concentration analysis.1-week washout period and administration of the alternate formulation.Multiple dosing: 22 male subjects were enrolled in this study, subjects fasted overnightfor at least 10 hours before dosing,then received a single 0.3g/capsule dose of test or reference drug(0.3g, q12 h, 7 days).Blood samples were collected day 4 to day 7 pre-dose and at 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 10 h, 12 h, 15 h and 24 hours after day 7 dosing for drug concentration analysis.1-week washout period and administration of the alternate formulation.RESULT AND CONCLUSION:22 healthy subjects single oral dosing under fasting condition, the relative bioavailability of AUC0â†'t and AUC0â†'∞ were 99.9±2.3% and 99.9±2.4% respectively.The AUC0â†'t, AUC0â†'∞ and Cmax of test and reference drug were evaluated by variance analysis and two one- side t test, there were not statistically different(P> 0.05). The 90% confidence intervals(CIs) for the AUC0â†'t, AUC0â†'∞, Cmax were 95.8% ~ 103.7%, 95.7% ~ 103.8% and 94.9% ~ 105.8%, respectively. As the 90% CIs between the test and reference formulation were within the 80%-125%, we concluded that the two formulations were bioequivalent.The 22 healthy subjects after single dosing under fasting condition would enroll in the single dosing under fed condition, the relative bioavailability of AUC0â†'t and AUC0â†'∞ were 99.9±1.7% and 100±1.8% respectively.The AUC0â†'t, AUC0â†'∞ and Cmax of test and reference drug were evaluated by variance analysis and two one- side t test, there were not statistically different(P> 0.05). The 90% confidence intervals(CIs) for the AUC0â†'t, AUC0â†'∞, Cmax were 96.4% ~102.3%, 96.7% ~102.7% and 92.9% ~101.9%, respectively. As the 90% CIs between the test and reference formulation were within the 80%-125%, we concluded that the two formulations were bioequivalent.22 male subjects received a single 0.3g/capsule dose of test or reference drug(0.3g, q12 h, 7 days). The relative bioavailability of AUCss was100.2±3.3%. The AUCss and Cmax of test and reference drug were evaluated by variance analysis and two one- side t test, there were not statistically different(P> 0.05). The 90% confidence intervals(CIs) for the AUCss and Cmax were 95.5% ~ 105.9% and 98.2% ~ 107%, respectively. As the 90% CIs between the test and reference formulation were within the 80%-125%, we concluded that the two formulations were bioequivalent.There were no SAE during the whole study. All the laboratory tests which did before and after the study, include routine blood test, urine routine, biochemical and electrocardiogram examination, were evaluated by variance analysis, there were no statistically significant difference(P > 0.05).