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Disposition of Piroxicam Following Transdermal Administration in Patients with Osteoarthritis

Background : Piroxicam(P) is usually administered once or twice a day for the treatment of arthritis. Since arthritis is a chronic disease, patients require a long term therapy with P, which results in a number of side effects such as gastrointestinal disorders and bleeding. In order to lessen these side effects and to increase patient's compliance, the P transdermal patch has been developed. The purpose of this study was to compare the disposition of transdermal P with that of oral P at steady state. Methods : A total of twenty patients (4 males and 16 females) aged 54 to 77 years with osteoarthritis were randomized and equally divided into 2 group. Group I was treated with $Trast^{TM}$ transdermal patch containing 48mg of P (manufactured by Sunkyong Pharm., Seoul) on the knee every other day for 14 days, and Group II received oral P 20mg once a day for 14 days. We collected plasma and tissue samples from Group I at 36 hrs after the last application of transdermal patch and from Group II at 12 hrs following the last oral dose. P Concentrations in plasma and tissues were analyzed by high-performance liquid chromatography(HPLC) with UV detection. Wilcoxon rank sum test was performed to evaluate the differences between the two formulations. Results : P concentration in plasma following transdermal administration was significantly lower compared to that of oral administration $(0.11{\pm}0.19\;vs.\;5.69{\pm}2.26{\mu}g/ml,\;p<0.01)$. However, there was no statistical difference in the synovial fluid between Group I and Group II $(5.44{\pm}0.36\;vs.\;5.37{\pm}3.72{\mu}g/ml,\;p=0.2483)$, while the inter-individual differences were lesser in Group I than in Group II (coefficient variation ; 6.6% vs. 69.3%). When compared to Group II, P concentrations In Group I were significantly lower in synovium, muscle, and adipose tissue $(0.0101{\pm}0.0148\;vs.\;0.0740{\pm}0.0249,0.0036{\pm}0.0021\;vs.\;0.0552{\pm}0.0341,and\;0.0034{\pm}0.0019\;vs.\;0.0256{\pm}0.0118{\mu}g/g;p<0.01)$ Conclusion : The plasma concentration in Group I was 50 times lower than that in Group II, but the synovial fluid concentration was comparable, suggesting that the transdermal patch would be expected to produce equivalent therapeutic effects and reduce systemic side effects.