Pharmacokinetic Properties and Antiinflammatory Activity of Ketoprofen Lotion

케토프로펜 로오숀의 약물동력학적 특성과 항염증작용

The pharmacokinetic properties and antiinflammatory activity of 3% ketoprofen lotion (ID-lotion), formulated with poloxamer 407, were evaluated using rats. For the pharmacokinetic study, the lotion, at the dose of 4.5 mg/kg, was applied on the dorsal skin of rats and the drug concentration in plasma was determined using an HPLC method. As references, ketoprofen suspended in saline was administered orally, and E-lotion, which is a 3% ketoprofen lotion in the Japanese market was applied transdermally. Following the transdermal application of ID-lotion and E-lotion, $C_{max}$ were 316 $\pm$22.3 ng/ml and 163 $\pm$ 12.2 ng/ml, respectively, at the same Tma of 2 hours postdose, while $C_{max}$ and $T_{max}$ after oral administration of the drug were 1,030$\pm$89.1 ng/ml and 0.25 hours, respectively. Relative bioavailabilities of ID-lotion and I-lotion were 69.3% and 34.2%, respectively. The antiinflammatory activity of the two 3% ketoprofen lotions was evaluated with carrageeneninduced edema method after 50 mg of the lotions was applied on the paw of rats. ID-lotion showed 67.6% inhibition of the edema formation, while I-lotion showed 34.\\\\`r%. The calculated ED5o after transdermal application of ID-lotion was 2.5 mg/kg, while that after oral administration was 7.0 mg/kg. Based on these results, the relative equiponderal availability of ID-lotion was 296% compared to the oral administration of ketoprofen.n.n.n.