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SAT0427 S- and R-flurbiprofen pharmacokinetics following repeated transdermal medication to healthy subjects
  1. G. Trummlitz1,
  2. H. Nell2,
  3. D. van Schalkwyk3,
  4. B. Rosenkranz4,
  5. P. Stonier5
  1. 1Pharmaconsulting PCGT, Warthausen, Germany
  2. 2Tiervlei Trial Centre, Cape Town
  3. 3Cape Town Data CC, Cape Town
  4. 4Department of Medicine, Division of Pharmacology, University of Stellenbosch, Cape Town, South Africa
  5. 5Amdipharm Plc, Basildon, United Kingdom

Abstract

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[1].

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.

  1. A.M. Taburet et al., J Clin Pharm Ther. 20(2):101-107.

Disclosure of Interest None Declared

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