密固达安全使用指南.ppt

Version11-Sep-07MA-*ZoledronicAcid:KeyPharmacologicalCharacteristicsTheuniquepharmacologicprofileofzoledronicacidmayexplainwhyitispossibletoachieveprofoundandsustainedsuppressionofboneresorptionwithasingle,lowdoseofbisphosphonate:Zoledronicacidhasahighbindingaffinityforbonemineral.1Thismaximizestheamountofdrugthatbindstoboneandislikelytominimizetheamountofdrugthatdiffusesfromboneafterbinding.ZoledronicacidisapotentinhibitorofFPPsynthase.2Thismaximizestheantiresorptivepotentialofthedrugandminimizesthetotalamountofdrugrequiredineachdose.Zoledronicacidhasahightherapeuticratio(resorptioninhibition:mineralizationinhibition)3andgoodrenaltolerability.4Thismaximizesthesafetyofthisbisphosphonateandallowsthepatient’stotalannualdosetobedeliveredinasingleadministration.References1. NancollasGH,TangR,PhippsRJ,etal.Novelinsightsintoactionsofbisphosphonatesonbone:differencesininteractionswithhydroxyapatite.Bone.2006,38:617-627.2. DunfordJE,ThompsonK,CoxonFP,etal.Structure-activityrelationshipsforinhibitionoffarnesyldiphosphatesynthaseinvitroandinhibitionofboneresorptioninvivobynitrogen-containingbisphosphonates.JPharmacolExpTher.2001;296:235-242.3. WidlerL,JaeggiKA,GlattM,etal.Highlypotentgeminalbisphosphonates.Frompamidronatedisodium(Aredia)tozoledronicacid(Zometa).JMedChem.2002;45:3721-3738.4. GreenJR,SeltenmeyerY,JaeggiKA,etal.Renaltolerabilityprofileofnovel,potentbisphosphonatesintwoshort-termratmodels.PharmacolToxicol.1997;80:225-230.HORIZON-PFTStudy2301SlideLibraryV43-May-07CONFIDENTIALHORIZON-PFTSlideLibrary-*输注后3天内发生的最常见不良事件(2%)总体上，在每次输注后的头3天内，唑来膦酸治疗者中有51.3%发生至少一种AE，而安慰剂组为26.3%。3天后最常见AE发生率在ZOL和安慰剂组之间无明显差异。开始于注射后3天内的AE为典型的一过性反应，任一次输注后早期发生的常见AE(≥5.0%)为发热、肌痛、流感样症状、头痛和关节痛。这些AE大部分在3天内缓解（唑来膦酸组的64.71%和安慰剂组的58.77%）。7天内