Background Flurbiprofen (fbp) is a chiral non-steroidal anti-inflammatory drug (NSAID) used as racemate in the treatment of rheumatism & non-arthritic pain. Topical formulations of NSAIDs have become popular for treatment of various acute & chronic, in particular localised, painful inflammatory conditions. Although activity of fbp is due mainly to its S-enantiomer, information on pharmacokinetics of fbp after topical administration is based on the measurement of racemic fbp.
Objectives The present study was performed to investigate the pharmacokinetics of S- and R-flurbiprofen (S-fbp & R-fbp) in 18 healthy subjects (9 female; 9 male) following the transdermal racemic flurbiprofen patch formulations AdoFeed® (Ado, test) and TransAct®LAT (Tra, reference). The primary objective of the study was to investigate the bioequivalence of the two formulations.
Methods The study was conducted in a randomised, open-label, crossover design with 2 treatment periods, each of 7 days, with 40 mg racemic fbp patches applied twice daily separated by a wash-out period of 7 days. During each treatment period blood sampling was conducted on days 1-10. A validated high performance liquid chromatography assay with tandem mass spectrometric detection was applied for quantification of S- & R-fbp. Primary endpoints to compare the extent & rate of absorption of fbp from the 2 formulations were: area under the plasma concentration vs. time curve during the last dosing interval (AUCτ), maximum plasma concentrations (Cmax,ss) & minimum plasma concentrations (Cmin,ss) at steady state of S-fbp.
Results AUCτ, Cmax,ss & Cmin,ss are listed for S-fbp from Ado and Tra and are compared to R-fbp:
Mean ± SD values for percentage peak trough fluctuation (%PTF) were for S-fbp from Ado: 50.264±16.529%, Tra: 45.836±14.886%; R-fbp from Ado: 64.550±20.421%, Tra: 61.105±16.425%, for time at Cmax,ss (Tmax): S-fbp from Ado: 2.726±2.245h, Tra: 2.332±1.414h; R-fbp from Ado: 2.222±1.478h, Tra: 1.889±1.641h and for apparent terminal elimination half-life (τ1/2): S-fbp from Ado: 9.720±2.736h, Tra: 9.656±2.421h; R-fbp from Ado: 6.902±2.596h, Tra: 7.207±2.607h.
For both transdermal formulations no serious adverse events (AEs) were reported, no subjects withdrew from the study due to AEs, and AEs were limited & similar in both groups.
Conclusions Bioequivalence with regard to rate and extent of absorption of fbp for AdoFeed® and TransAct®LAT transdermal products, applied twice daily for 7 days, was concluded based on the primary pharmacokinetic variables AUCτ, Cmax,ss and Cmin,ss of S-fbp. For all 3 variables the 90% CI for the test/reference ratio was within the equivalence range of 80-125%. For both products AUC, Cmax,ss, Cmin,ss, %PTF & τ1/2 for S-fbp were between 20-50% higher than for R-fbp, indicating a lower clearance for S-fbp; in contrast the absorption of fbp seems to be not stereoselective.
A.M. Taburet et al., J Clin Pharm Ther. 20(2):101-107.
Disclosure of Interest None Declared
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