Population pharmacokinetic modeling of flurbiprofen, the active metabolite of flurbiprofen axetil, in Chinese patients with postoperative pain

Dong

et al. 2021

Clin Exp Pharma Physio

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.

Section: Discussionsupporting

confidence: 88%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Dong

et al. 2021

Clin Exp Pharma Physio

“…In addition, most patients refused to endure the acute pain and requested post-operative analgesia in the preliminary experiment. In order to enhance the comfort level of patients and reduce doctor-patient disputes, patients in two groups were intravenously given flurbiprofen axetil (1 mg/kg) for post-operative analgesia at the end of the operation (40). The half-life of flurbiprofen axetil is ~5.8 h (41), and therefore, the pain within the first 6 h after the operation was not evaluated.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of intravenous lidocaine in improving post‑operative nausea, vomiting and early recovery after laparoscopic gynaecological surgery

et al. 2019

Post-operative nausea and vomiting (PONV) is a major peri-operative complication. It has numerous adverse consequences that seriously affect the post-operative recovery of patients. The aim of the present study was to investigate the efficacy of intravenous lidocaine in improving PONV and recovery after laparoscopic gynaecological surgery. A total of 40 patients were randomly assigned to 2 groups: Group L (lidocaine group) and Group C (control group). The patients in Group L received intravenous lidocaine throughout the operation, while patients in Group C were given a saline infusion. Vital signs, recovery time, extubation time, dosage of remifentanil, first flatus time and defecation time of each patient were recorded. The incidence of PONV after surgery was also recorded. The recovery of the patients was evaluated by using the quality of recovery score (QoR-40). The total dose of remifentanil was significantly lower in Group L (P<0.05). However, the recovery time and extubation time were shorter in Group C (P<0.05). The first flatus time and defecation time were longer in Group C (P<0.05). The mean arterial pressure and heart rate in Group L were lower and more stable (P<0.05). At 6 h after surgery, the incidence of PONV was significantly lower in Group L vs. that in Group C (P<0.05). The QoR-40 score in Group C was significantly lower at 1 and 3 days after the operation compared with that in Group C (P<0.05). In conclusion, intravenous lidocaine administered to patients undergoing laparoscopic gynaecological surgery may reduce PONV and supports their early recovery [trial registration number in Chinese Clinical Trial Registry: ChiCTR-IOR-17010782 (March 5, 2017)].

“…p < 0.05 was considered statistically significant. Pharmacokinetic modeling was conducted with Drug and Statistics (DAS, version 2.0, Mathematical Pharmacology Professional Committee of China, Shanghai, China) using a one-compartment model (Zhang et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

The Comparison of Plasma and Cerebrospinal Fluid R(−)- and S(+)-Flurbiprofen Concentration After Intravenous Injection of Flurbiprofen Axetil in Human Subjects

et al. 2021

Self Cite

Background: Flurbiprofen axetil is a prodrug that releases the active substance through enzymatic removal of the ester moiety. It is formulated through encapsulation in a lipid microsphere carrier, and widely used to treat perioperative pain. Here, we studied the distribution of R (−)- and S (+)-flurbiprofen in human plasma and cerebrospinal fluid (CSF) after intravenous injection of flurbiprofen axetil.Methods: A total of 70 adult patients undergoing elective lower limb surgery under spinal anesthesia were given a single intravenous injection of 100-mg flurbiprofen axetil. The patients were randomly assigned to 10 groups for plasma and CSF sampling at 10 time points (5–50 min) after subarachnoid puncture and before actual spinal anesthesia. R (−)- and S (+)-flurbiprofen and CSF/plasma ratio were determined by liquid chromatography–tandem mass spectrometry.Results: R (−)-flurbiprofen concentration ranged from 2.01 to 10.9 μg/mL in plasma and 1.46–34.4 ng/mL in CSF. S (+)-flurbiprofen concentration ranged from 1.18 to 10.8 μg/mL in plasma and from 2.53 to 47 ng/mL in CSF. In comparison to S (+)-flurbiprofen, R (−)-flurbiprofen concentration was significantly higher in plasma at all time points (p < 0.05) except at 30 or 40 min, and lower in CSF at all time points (p < 0.05) except at 10, 15 and 40 min. Analysis after correcting drug concentration for body mass index also revealed higher plasma and lower CSF R (−)-flurbiprofen concentration. In comparison to S (+)-flurbiprofen, AUC0–50 for R (−)-flurbiprofen was larger in plasma and smaller in CSF (p < 0.05 for both), and accordingly smaller CSF/plasma AUC0–50 ratio (p < 0.05). There was a positive correlation between R (−)-flurbiprofen concentration and S (+)-flurbiprofen concentration in plasma (r = 0.725, p < 0.001) as well as in CSF (r = 0.718, p < 0.001), and a negative correlation between plasma and CSF concentration of S (+)-flurbiprofen (r = −0.250, p = 0.037), but not R (−)-flurbiprofen.Conclusion: Distribution of R (−)- and S (+)-flurbiprofen in plasma and CSF differed significantly. Penetration of R (−)-flurbiprofen into the CNS was lower than S (+)-flurbiprofen.