简介：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.

简介：本文研究了双波长差示一阶导数分光光度法运用于作为对照品的一氧化碳（ＣＯ）饱和水浓度标定及定性与定量测定微粒体代谢中生成的一氧化碳的方法。本法的优点在于能显著消除试样本底干扰，大大提高了定量准确性及灵敏度。在ＣＯ浓度２～１０μｍｏｌ·Ｌ１范围内与导数光谱峰（４１５ｎｍ）和谷（４２６ｎｍ）之间距离（Ｄ）呈良好线性关系，ｒ＝０．９９９９（ｎ＝５），回归方程Ｃ（ｍｍｏｌ·Ｌ１）＝１７．６Ｄ０．４。最低检测浓度低于０．１μｍｏｌ·Ｌ１ＣＯ。系统回收率和加样回收率（Ｘ±ＲＳＤ）分别为１０２．１±２．９％（ｎ＝７）和７９．７±６．８％（ｎ＝１２）；日内、日间精密度（ＲＳＤ）分别为４．４％（ｎ＝１８）和６．１％（ｎ＝１６）。将本法用于４个三卤苯胺和一个三卤苯的体外代谢测定，结果表明，仅２，４，５三氟苯胺在体外能被大鼠肝微粒体、ＮＡＤＰＨ和分子氧代谢生成一氧化碳。苯巴比妥和地塞米松等肝药酶诱导剂能显著提高一氧化碳的代谢转化速率，它们分别为空白对照组的３或８倍。