| Meloxicam is a non-steroidal anti-inflammatory drug which was widely used to treatpatients with rheumatoid arthritis and osteoarthritis. Selective COX-2 inhibitors suchas me1oxicam are thought to hav'e feYVer adverse gastrointestinal reactions than othernon-steroidal anti-inflammatory drugs. But adverse reactions induced by meloxicamorally or intravenously administered recently could aIso be found. Meloxicam gel(Me1 G) adrninistered thIough cutaneously (tc ) could avoid over-high serum drugconcentration, which is relevant to adverse reactions, and may be a new preparationx"ith less toxic and more effective. The therapeutic effect of Mel G was studied by'means of adjuvant arthritis(AA) model which was induced by intradermal injection ofFreund's complete adjuvant(FCA). The effects of Mel G on rat AA were observedfOllowing Mel G tc. Me1 G (3.75' 7.5' l5 mg. kg-' ) significantly inhibited primaIyand secondary inflanunation of AA rats. Compared with intragastric injection (ig)Me1, Mel G had less adver5e reactions (such as ulcer index) and no effect tvereobseri!ed on tx-eight gain of AA rats.A high perfOrmance liquid cbIomatography (HPLC ) method t'ith ultraviolet detectionwas set up to determine the concentration of Mel in serum and local tissue, the mobilephase consisted of methanol: Water f Acetic acid t Acetonitrile = 600: 500: 20f 50 witha flow rate of l .0 ml. min-1 ) a constan temperature oven was set at 40C and the UVabsorbance detector was set at 355nm, Under this condition, Mel in serum could bewell separated. The limit of detection was l.95 ng. A good linearity of Mel tt'asobtained from 0.039 ng. ml-I to l0ng. m1-1 t'-ith r=0.9998 (P (0.05 ), The recovery inserum was between 85.67% and 95.09%, and the recovery in local tissue was betWeen4%4tt a f}k4xz + 4tisak80. l 3% and 94.56%. All of these showed HPLC method fitted for ana1ytic requirementof Mel preparation. Then AA model t'as used to study the relationship betxveentherapeutic effect and serum or local tissue concentration of Mel G in rats. The resultsshot'.ed that the concentration of NIel G t"as lower in serum and higher in local tissuethan that of Mel tablets. A significant 1inear correlation in a negative manner existedbettt'een local tissue concentration of Mel G and hindpaw sxx.el1ing volume, xx1ith thecorrelation coefficient rv -0.7459, P<0.05.The pharmacokinetics of Mel G in rabbits after a single dose of 3.75, 7.5 and1 5mg. kg-' tc was also studied, HPLC method xtas used to determine the concentrationof Mel in serum, The results of the pharmacokinetic study of Me1 G showed that itexhibited first order kinetic characteristics. The profile of the serum concentration-timecurves of Me1 G after a sing1e dose of 3.75, 7.5 and l5rng. kg-' tc was fitted tott'-o-compartment model. Short T1,2ka indicated that Mel G t"as ea5y to be absorbed.Main pharmacokinetic parameters of MeI G after singIe dose transdermaladministration in five rabbits as follow:Mel G 3.75mg. kg-': Tl/2k. 0' 12l5i0. l506h, T1/2k, 7.97f2.56h, T.. 1 h,C.,. l .42t0.38 ll g. ml-1, AUCo~:4 5'9521 .47 P g. h. ml-':Mel G 7.5 mg. kg-': Tl/2k. 0'205lr0.2769 h, Tl;2k, l2'88i10.38 h, T... l h,C.. 2'30I0.7l ll g. ml-l, AUCo--24 l2'98I5.08 ll g. h. ml-l:Mel G l 5 mg. kg-': Tl/2k, 0'2792I0.2929 h, Tl/2k, 22' l3f32.l8 h, T..l '210.45 h,C.. 6' 151l .47 ll g. ml-l, AUCo~24 22' l6I6.52 ll g. h. ml-1.In a t'.ord, Mel G is a new preparation for treatment rheurnatoid arthIitis xx'ith less toxicand more effecti1'e. |
PDF Full Text Request