Pharmacokinetic comparison of oral and local action transcutaneous flurbiprofen in healthy volunteers

Abstract

Flurbiprofen is a propionic acid-derived non-steroidal anti-inflammatory drug (NSAID) used widely in the treatment of rheumatism and non-arthritic pain. The pharmacokinetics of topically and orally administered flurbiprofen were compared in a two-part, open study involving healthy adult volunteers. In the first (cross-over) part of the study, 12 Caucasians were randomized to receive either a single oral dose of 50 mg flurbiprofen or a single topical application of a novel 40 mg flurbiprofen-containing patch on the right wrist for 12 h. In the second part of the study, each subject applied a flurbiprofen-containing patch twice daily to the same wrist for 7 days. Plasma concentrations of flurbiprofen and urinary concentrations of the NSAID and its metabolites were measured by high-performance liquid chromatography assay, to enable comparison of the pharmacokinetic parameters for delivery of the drug by both routes. Maximum concentrations of the NSAID in plasma (Cmax) were much lower after a single application of the topical 40 mg flurbiprofen patch than after a single oral dose of 50 mg of the NSAID (mean +/- SD: 43 +/- 16 ng/ml versus 5999 +/- 1300 ng/ml, respectively). After repeated application of the topical patch, Cmax increased only slightly to 103 +/- 57 ng/ml. The mean relative bioavailability of flurbiprofen from the patch was 3.5 +/- 1.7%, calculated from plasma area under the curve data and 4.4 +/- 2.8% from urinary excretion data.(ABSTRACT TRUNCATED AT 250 WORDS)