Percutaneous Absorption and Metabolism of Ketoprofen Isopropyl Ester via Excised Nude Mouse‘s and Monkey’s Skin

(整期优先)网络出版时间:2003-01-11
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Aim:Tostudypercutaneousabsorptionandmetabolismofketoprofenisopropylester(KPE)viaexcisednudemouse'sandmonkey'sskin.Methods:Excisedskinwaspreparedbysurgicalexcisionandenzymedigestion.Sideby-sidediffusioncellswereusedforinvitropermeationstudies.TheconcentrationsofKPEanditsmetaboliteinsampleswereassayedbyHPLC.Results:AllKPEpenetrationthroughwholethicknessskinandstrippedskinwasmetabolizedtoketoprofen(KP).theconcentrationofwhichinthereciiversolutionincreasedlinearlywithtime.Astothenudemouseskin.thesteady-statefluxofKPthroughwholethicknessskinwas2.5timesthatofKPEthroughthewhloethicknessskin,buttheKPandKPEremaininginthewholethicknessskinafterthefinishingofKPEpenetrationwas22.2timesincomperedwiththeKPremaininginthewholethicknessskinafterthefinshingofKPpenetration.TherateofformationofthesteadystateKPfromKPEthroughtdermiswassignificantlylowerthanthatofKPEthroughthewholethicknessskin.Inhemonkeyskin,therateofformationofthesteady-stateKPfromKPEthroughthewholethicknessskinwas0.7timesthatfromKPEthroughstrippedskin.TheKPandKPEremaininginthewholethicknessskinafterthefinishingofKPEpenetrationwas2.0timethatinthestrippedskinafterthefinishingofKPEpenetration.Therateoffornationofthesteady-stateKPfromKPEthroughdermiswaslowerthanthatfromKPEthroughthewholethicknessskinandthestrippedskin.theKPremainingindermisafterthefinsihingofKPEpenetrationwasalsosignificantlylowerthantheKPremaininginthewholethicknessskinandthestrippedskinafterthefinishingofKPEpenetration.Conclusion:KPestersareofbenefittoimporovethelocalactionofKP.andskinesterasemetabolismmainlydevelopsintheepidermis.