Mounting evidence demonstrates that CYP2B6 plays a much larger role in human drug metabolism than was previously believed.The discovery of multiple important substrates of CYP2B6 as well as polymorphic differences has...Mounting evidence demonstrates that CYP2B6 plays a much larger role in human drug metabolism than was previously believed.The discovery of multiple important substrates of CYP2B6 as well as polymorphic differences has sparked increasing interest in the genetic and xenobiotic factors contributing to the expression and function of the enzyme.The expression of CYP2B6 is regulated primarily by the xenobiotic receptors constitutive androstane receptor(CAR) and pregnane X receptor(PXR) in the liver.In addition to CYP2B6,these receptors also mediate the inductive expression of CYP3A4,and a number of important phase II enzymes and drug transporters.CYP2B6 has been demonstrated to play a role in the metabolism of 2%–10% of clinically used drugs including widely used antineoplastic agents cyclophosphamide and ifosfamide,anesthetics propofol and ketamine,synthetic opioids pethidine and methadone,and the antiretrovirals nevirapine and efavirenz,among others.Significant inter-individual variability in the expression and function of the human CYP2B6 gene exists and can result in altered clinical outcomes in patients receiving treatment with CYP2B6-substrate drugs.These variances arise from a number of sources including genetic polymorphism,and xenobiotic intervention.In this review,we will provide an overview of the key players in CYP2B6 expression and function and highlight recent advances made in assessing clinical ramifications of important CYP2B6-mediated drug–drug interactions.展开更多
目的探讨依非韦伦致药品不良反应(ADR)的分布规律。方法检索PubMed、Embase、Web of Science、中国知网、万方数据库及维普数据库中依非韦伦致ADR的个案报道及临床试验研究,并对依非韦伦的ADR进行汇总分析。检索时间为建库至2020年10月3...目的探讨依非韦伦致药品不良反应(ADR)的分布规律。方法检索PubMed、Embase、Web of Science、中国知网、万方数据库及维普数据库中依非韦伦致ADR的个案报道及临床试验研究,并对依非韦伦的ADR进行汇总分析。检索时间为建库至2020年10月31日。结果共纳入文献93篇,其中个案报道90篇,临床试验研究3篇。共收集病例244例,其中男性161例(66.0%),女性83例(34.0%),21~50岁患者居多(76.6%),ADR发生中位时间为1.6个月;累及的器官或系统主要有神经系统(58.2%)、皮肤及其附件(16.8%)、内分泌系统(10.2%)和消化系统(6.6%)等。结论依非韦伦所致的ADR涉及多个系统,且严重程度不同,临床应用应结合患者个体情况,加强ADR监测,保障患者用药安全。展开更多
分别以聚维酮K29/32、共聚维酮S-630、聚乙烯己内酰胺-聚乙酸乙烯酯-聚乙二醇接枝共聚物(Soluplus)以及3个规格的醋酸羟丙甲纤维素琥珀酸酯(HPMCAS,规格L、M和H)为载体材料,采用喷雾干燥技术制备依非韦伦固体分散体。以120 min 的动力...分别以聚维酮K29/32、共聚维酮S-630、聚乙烯己内酰胺-聚乙酸乙烯酯-聚乙二醇接枝共聚物(Soluplus)以及3个规格的醋酸羟丙甲纤维素琥珀酸酯(HPMCAS,规格L、M和H)为载体材料,采用喷雾干燥技术制备依非韦伦固体分散体。以120 min 的动力溶解度为指标考察,筛选出增溶效果和抑晶效果较优的载体材料,并用全因子设计优化喷雾干燥的工艺参数。通过差示扫描量热(DSC)法、X射线粉末衍射(XRPD)法和红外光谱(FT-IR)法对优化所得的固体分散体进行物相鉴别。结果表明,L规格的HPMCAS 增溶效果最好;依非韦伦与HPMCAS L 的质量比为1∶3时制得的固体分散体在pH6.8 磷酸盐缓冲溶液中120min 的动力溶解度达到(955.97±5.13)μg/ml,比原料药提高了约66.7 倍;喷雾干燥工艺参数中泵的流速越慢、氮气流量越大,制得的固体分散体动力溶解度越高。DSC 和XRPD 结果表明依非韦伦以无定形分散在载体材料中,FT-IR 显示依非韦伦与载体材料分子之间以氢键结合。加速试验[40℃、相对湿度75%]结果表明HPMCAS L 固体分散体在6个月内较稳定;大鼠体内药动学试验表明,该固体分散体的cmax 和AUC0→t分别为原料药的1.98 和1.79 倍。本试验表明以HPMCAS L为载体制备的依非韦伦固体分散体可显著提高药物的溶解度和口服生物利用度。展开更多
基金supported by research grants from the U.S. National Institute of Health (DK061652 and GM107058)
文摘Mounting evidence demonstrates that CYP2B6 plays a much larger role in human drug metabolism than was previously believed.The discovery of multiple important substrates of CYP2B6 as well as polymorphic differences has sparked increasing interest in the genetic and xenobiotic factors contributing to the expression and function of the enzyme.The expression of CYP2B6 is regulated primarily by the xenobiotic receptors constitutive androstane receptor(CAR) and pregnane X receptor(PXR) in the liver.In addition to CYP2B6,these receptors also mediate the inductive expression of CYP3A4,and a number of important phase II enzymes and drug transporters.CYP2B6 has been demonstrated to play a role in the metabolism of 2%–10% of clinically used drugs including widely used antineoplastic agents cyclophosphamide and ifosfamide,anesthetics propofol and ketamine,synthetic opioids pethidine and methadone,and the antiretrovirals nevirapine and efavirenz,among others.Significant inter-individual variability in the expression and function of the human CYP2B6 gene exists and can result in altered clinical outcomes in patients receiving treatment with CYP2B6-substrate drugs.These variances arise from a number of sources including genetic polymorphism,and xenobiotic intervention.In this review,we will provide an overview of the key players in CYP2B6 expression and function and highlight recent advances made in assessing clinical ramifications of important CYP2B6-mediated drug–drug interactions.
文摘目的探讨依非韦伦致药品不良反应(ADR)的分布规律。方法检索PubMed、Embase、Web of Science、中国知网、万方数据库及维普数据库中依非韦伦致ADR的个案报道及临床试验研究,并对依非韦伦的ADR进行汇总分析。检索时间为建库至2020年10月31日。结果共纳入文献93篇,其中个案报道90篇,临床试验研究3篇。共收集病例244例,其中男性161例(66.0%),女性83例(34.0%),21~50岁患者居多(76.6%),ADR发生中位时间为1.6个月;累及的器官或系统主要有神经系统(58.2%)、皮肤及其附件(16.8%)、内分泌系统(10.2%)和消化系统(6.6%)等。结论依非韦伦所致的ADR涉及多个系统,且严重程度不同,临床应用应结合患者个体情况,加强ADR监测,保障患者用药安全。
