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.

Effect of flurbiprofen axetil combined with “Cocktail” therapy on opioid dosage in patients after total knee arthroplasty

“…In contrast, flurbiprofen axetil can inhibit cyclooxygenase to reduce arachidonic acid to produce prostaglandins, and at the same time inhibit the production of central prostaglandins, thereby reducing the sensitization of the central and peripheral nervous systems and achieving analgesic effects. 20 , 21 It was shown in a study by Wang J et al 22 that flurbiprofen axetil can be targeted to accumulate on surgical incisions and inflammation sites, with rapid onset, and the blood concentration can reach the peak 5-10 minutes after intravenous administration. With the combination of two analgesic regimens, the analgesic effect can be synergistically exerted and the analgesic effect can be optimized.…”

Comparison of in vivo pharmacokinetic behaviors of R‐ and S‐flurbiprofen after intravenous injection of flurbiprofen axetil

“…Flurbiprofen axetil (FA) is a non-steroidal antiinflammatory drug (NSAID), and it exerts antiinflammation and antinociception effects with lipid microspheres as drug carriers. 1,2 It was proposed to be used in the postoperative pain management because of the selective accumulation in surgical incision before its hydrolysis to active flurbiprofen (FP) by carboxylesterase in plasma. 1 The chemical structures of FA and FP are shown in Figure 1.…”

Determination of flurbiprofen in rat plasma using ultra‐high performance liquid chromatography–tandem mass spectrometry and its application in a pharmacokinetic study

“…Compared with other methods, LC–MS/MS had a higher sensitivity and selectivity. However, the LC–MS/MS method was also limited due to the following factors: time‐consuming and arduous liquid–liquid extraction sample preparation (Lee et al, 2014), requirement of a large volume of sample (Mei et al, 2015), and no complete method validation (Wang et al, 2021). A sensitive ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method has been reported for the determination of flurbiprofen in rat plasma (Yaman et al, 2021).…”