AIM To evaluate the utility of patch test and cross-sensitivity patterns in patients with adverse cutaneous drug reactions(ACDR) from common anticonvulsants. METHODS Twenty-four(M:F = 13:11) patients aged 18-75 years ...AIM To evaluate the utility of patch test and cross-sensitivity patterns in patients with adverse cutaneous drug reactions(ACDR) from common anticonvulsants. METHODS Twenty-four(M:F = 13:11) patients aged 18-75 years with ACDR from anticonvulsants were patch tested 3-27 mo after complete recovery using carbamazepine, phenytoin, phenobarbitone, lamotrigine, and sodium valproate in 10%, 20% and 30% conc. in pet. after informed consent. Positive reactions persisting on D3 and D4 were considered significant. RESULTS Clinical patterns were exanthematous drug rash with or without systemic involvement(DRESS) in 18(75%), Stevens-Johnsons syndrome/toxic epidermal necrolysis(SJS/TEN) overlap and TEN in 2(8.3%) patients each, SJS and lichenoid drug eruption in 1(4.2%) patient each, respectively. The implicated drugs were phenytoin in 14(58.3%), carbamazepine in 9(37.5%), phenobarbitone in 2(8.3%), and lamotrigine in 1(4.7%) patients,respectively. Twelve(50%) patients elicited positive reactions to implicated drugs; carbamazepine in 6(50%), phenytoin alone in 4(33.3%), phenobarbitone alone in 1(8.3%), and both phenytoin and phenobarbitone in 1(8.33%) patients, respectively. Cross-reactions occurred in 11(92%) patients. Six patients with carbamazepine positive patch test reaction showed cross sensitivity with phenobarbitone, sodium valproate and/or lamotrigine. Three(75%) patients among positive phenytoin patch test reactions had cross reactions with phenobarbitone, lamotrigine, and/or valproate. CONCLUSION Carbamazepine remains the commonest anticonvulsant causing ACDRs and cross-reactions with other anticonvulsants are possible. Drug patch testing appears useful in DRESS for drug imputability and cross-reactions established clinically.展开更多
透皮贴剂作为应用广泛但开发复杂的仿制药剂型,其临床生物等效性试验开展难度较高,针对此,监管机构鼓励采用生理药代动力学(physiologically based pharmacokinetic,PBPK)模型引导研发,以降低成本并提升成功率。透皮贴剂的PBPK建模关键...透皮贴剂作为应用广泛但开发复杂的仿制药剂型,其临床生物等效性试验开展难度较高,针对此,监管机构鼓励采用生理药代动力学(physiologically based pharmacokinetic,PBPK)模型引导研发,以降低成本并提升成功率。透皮贴剂的PBPK建模关键影响因素包括药物特性、制剂系统与机体差异。药物因素方面,定量结构-性质关系(quantitative structure-property relationship,QSPR)模型基于相对分子质量、脂水分配系数(LogP)等参数预测分配与扩散系数;机制模型通过解析多层皮肤结构阐明渗透动力学过程。制剂系统中,骨架型与储库型贴剂的释放差异可通过多相多层皮肤吸收机制(multiphase multilayered mechanistic dermal absorption,MPML MechDermA)模型模拟,涵盖溶出、沉淀及载体蒸发等关键过程。机体差异上,皮肤厚度、pH值、附属器密度及病理状态等显著影响渗透效率,模型需结合年龄、性别、种族等变量校准。模型整合基于菲克定律构建隔室间药物转运方程,支持体外-体内外推(in vitro to in vivo extrapolation,IVIVE)。本文系统综述透皮贴剂开发的PBPK建模方法及其影响因素,有望减少动物实验并加速临床转化。展开更多
中枢神经系统疾病分类复杂且危害严重,由于特殊生理结构血-脑屏障(blood-brain barrier,BBB)的存在,中枢神经系统疾病的治疗在药物递送方面存在较大困难。经皮给药系统(transdermal drug delivery system,TDDS)作为一种新型药物递送系统...中枢神经系统疾病分类复杂且危害严重,由于特殊生理结构血-脑屏障(blood-brain barrier,BBB)的存在,中枢神经系统疾病的治疗在药物递送方面存在较大困难。经皮给药系统(transdermal drug delivery system,TDDS)作为一种新型药物递送系统,通过皮肤将药物送入血液循环,近年来在中枢神经系统疾病的治疗中发挥了巨大作用。其中透皮贴剂由于其无痛、给药方便等独特优势,具有良好的患者依从性和治疗效果,显著降低首过效应和不良反应。文章综述了透皮贴剂在神经退行性疾病以及精神疾病等中枢神经系统疾病治疗中的应用现状,重点探讨了纳米载体、微针技术等新型技术在提升药物递送效率方面的研究进展。但个体差异及长期用药安全性等仍是目前亟需解决的问题,未来研究应着重于新型递药技术开发及临床转化应用,以推动TDDS在中枢神经系统疾病治疗中的进一步发展。展开更多
文摘AIM To evaluate the utility of patch test and cross-sensitivity patterns in patients with adverse cutaneous drug reactions(ACDR) from common anticonvulsants. METHODS Twenty-four(M:F = 13:11) patients aged 18-75 years with ACDR from anticonvulsants were patch tested 3-27 mo after complete recovery using carbamazepine, phenytoin, phenobarbitone, lamotrigine, and sodium valproate in 10%, 20% and 30% conc. in pet. after informed consent. Positive reactions persisting on D3 and D4 were considered significant. RESULTS Clinical patterns were exanthematous drug rash with or without systemic involvement(DRESS) in 18(75%), Stevens-Johnsons syndrome/toxic epidermal necrolysis(SJS/TEN) overlap and TEN in 2(8.3%) patients each, SJS and lichenoid drug eruption in 1(4.2%) patient each, respectively. The implicated drugs were phenytoin in 14(58.3%), carbamazepine in 9(37.5%), phenobarbitone in 2(8.3%), and lamotrigine in 1(4.7%) patients,respectively. Twelve(50%) patients elicited positive reactions to implicated drugs; carbamazepine in 6(50%), phenytoin alone in 4(33.3%), phenobarbitone alone in 1(8.3%), and both phenytoin and phenobarbitone in 1(8.33%) patients, respectively. Cross-reactions occurred in 11(92%) patients. Six patients with carbamazepine positive patch test reaction showed cross sensitivity with phenobarbitone, sodium valproate and/or lamotrigine. Three(75%) patients among positive phenytoin patch test reactions had cross reactions with phenobarbitone, lamotrigine, and/or valproate. CONCLUSION Carbamazepine remains the commonest anticonvulsant causing ACDRs and cross-reactions with other anticonvulsants are possible. Drug patch testing appears useful in DRESS for drug imputability and cross-reactions established clinically.
文摘透皮贴剂作为应用广泛但开发复杂的仿制药剂型,其临床生物等效性试验开展难度较高,针对此,监管机构鼓励采用生理药代动力学(physiologically based pharmacokinetic,PBPK)模型引导研发,以降低成本并提升成功率。透皮贴剂的PBPK建模关键影响因素包括药物特性、制剂系统与机体差异。药物因素方面,定量结构-性质关系(quantitative structure-property relationship,QSPR)模型基于相对分子质量、脂水分配系数(LogP)等参数预测分配与扩散系数;机制模型通过解析多层皮肤结构阐明渗透动力学过程。制剂系统中,骨架型与储库型贴剂的释放差异可通过多相多层皮肤吸收机制(multiphase multilayered mechanistic dermal absorption,MPML MechDermA)模型模拟,涵盖溶出、沉淀及载体蒸发等关键过程。机体差异上,皮肤厚度、pH值、附属器密度及病理状态等显著影响渗透效率,模型需结合年龄、性别、种族等变量校准。模型整合基于菲克定律构建隔室间药物转运方程,支持体外-体内外推(in vitro to in vivo extrapolation,IVIVE)。本文系统综述透皮贴剂开发的PBPK建模方法及其影响因素,有望减少动物实验并加速临床转化。
文摘中枢神经系统疾病分类复杂且危害严重,由于特殊生理结构血-脑屏障(blood-brain barrier,BBB)的存在,中枢神经系统疾病的治疗在药物递送方面存在较大困难。经皮给药系统(transdermal drug delivery system,TDDS)作为一种新型药物递送系统,通过皮肤将药物送入血液循环,近年来在中枢神经系统疾病的治疗中发挥了巨大作用。其中透皮贴剂由于其无痛、给药方便等独特优势,具有良好的患者依从性和治疗效果,显著降低首过效应和不良反应。文章综述了透皮贴剂在神经退行性疾病以及精神疾病等中枢神经系统疾病治疗中的应用现状,重点探讨了纳米载体、微针技术等新型技术在提升药物递送效率方面的研究进展。但个体差异及长期用药安全性等仍是目前亟需解决的问题,未来研究应着重于新型递药技术开发及临床转化应用,以推动TDDS在中枢神经系统疾病治疗中的进一步发展。
