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We have evaluated the percutaneous penetration of felbinac following application of topical patches using a microdialysis technique, and have examined correlations with pharmacological effects. A linear microdialysis probe with a 20-mm dialysis fibre was inserted into the skin of anaesthetized rats. Probe perfusion was started at 2.0 microL min(-1) with physiological saline and after a 60-min baseline sampling of dialysate, 0.1 mL croton oil was applied to the skin surface at a concentration of 8%, v/v. A felbinac patch was then applied to the same point 60 min thereafter and dialysate was sampled at 60-min intervals up to 300 min after patch application, for determination of concentrations of felbinac and prostaglandin (PG) E2. Analgesic effects of felbinac patches in an iodoacetateinduced osteoarthritis model and an incisional pain model were evaluated using the weight bearing method. After application of patches, felbinac penetration into the skin was rapid, maximum concentrations in the dialysates with 0.07, 0.5 and 3.5% w/w felbinac patches being 0.046+/-0.02, 0.104+/-0.06 and 0.244+/-0.2 microg mL(-1), respectively. Dermal administration of croton oil caused an increment in PGE2 levels, which was significantly decreased by 0.5 and 3.5% felbinac patches 2-5 h after application. In pharmacological studies, 3.5% felbinac patches suppressed pain-associated behaviour induced by iodoacetate injection and plantar incision. These results suggested that the transdermal patch containing 3.5% felbinac may become a useful formulation.

The aim of this paper is to provide a simple and easy method for determination of meloxicam in rat muscle and plasma, based on dissolution of tissue samples with Solvable TM and measurement with a column-switching high performance liquid chromatographic system. After tissue and plasma samples were extracted with Solvable TM and methanol, samples were injected into a precolumn (Hypersil ODS) in 0.05 M phosphate buffer (pH 3), and after clean-up and enrichment the analytes were transferred to an analytical column (YMC Pack Pro C18) by backflushing with 0.05 M phosphate buffer (pH 6)-methanol (60:40, v/v). The eluate was monitored with a UV-detector set at 360 nm. Coefficients of determination (r 2) for muscle and plasma were both more than 0.999. The limits of quantification (LOQ) in muscle and plasma were 50 ng/g and 20 ng/mL, respectively. The accuracy and precision were achieved in the range of 50-2500 ng/g in muscle and 20-2500 ng/mL in plasma. Our method could be successfully applied to evaluate the pharmacokinetics of topically administrated meloxicam.