Evaluation of bioequivalence of two flurbiprofen axetil injections: A randomized, open‐label, double‐cycle, and crossover study

Abstract

Flurbiprofen is a non‐steroidal anti‐inflammatory drug. We evaluated the bioequivalence of a new formulation of flurbiprofen axetil for injection and the reference drug ROPION (another kind of flurbiprofen axetil injection marketed for use) in healthy Chinese subjects. This is a single‐centre, randomized, open‐label, single‐dose, two period crossover bioequivalence study. Each subject received a single intravenous injection at the dose of 50 mg under fasting. The drug was dissolved in 100 mL normal saline, and the injection was completed in 15 minutes. There was a 7‐day washout period between the two administrations. The plasma concentrations of flurbiprofen were measured by LC‐MS/MS, and descriptive statistics were used to describe the safety outcomes including adverse events (AEs) and adverse drug reactions (ADRs). Twenty‐four subjects were enrolled in this study. Mean values of primary PK parameters (Tmax, Cmax, AUC0‐t, AUC0‐∞, λz, T1/2) were similar (P > 0.05). Tmax for both products is 0.3 hours. The 90% confidence intervals (CIs) for peak concentration Cmax ranged between 96.87% and 100.42%, and the area under curve AUC0‐t and AUC0‐∞ ranged between 99.09% and 104.29% and 98.97% and 104.29%, respectively. The 90% CIs for the geometric means and ratios of primary PK endpoints of flurbiprofen axetil injection to reference drug ranged between 98.97% and 104.29%. The adverse event rate of the test product was 8.3% and no serious adverse events (SAE) occurred in this clinical study. We concluded that the test product and the reference drug were bioequivalent and the safety was high in healthy Chinese subjects.