银杏叶片对人药物代谢酶CYP2A6、XO和NAT2活性的影响

目的探讨银杏叶片对人肝脏药物代谢酶CYP2A6、XO和NAT2活性的影响,预测银杏叶片与常用药物的相互作用,指导临床合理用药.方法以咖啡因作为药物代谢酶CYP2A6、XO和NAT2的探针药物,以反相高效液相梯度洗脱法测定30名受试者服用银杏叶前后人尿液内咖啡因5种主要代谢物的相对含量,采用代谢物的比率分别评价人肝脏药物代谢酶CYP2A6、XO和NAT2活性的变化.结果受试者服药前CYP2A6、XO和NAT2平均活性为0.227±0.076、0.723±0.060和0.447±0.172;服用银杏叶片28d后CYP2A6、XO和NAT2平均活性为0.227±0.072、0.728±0.074和0.391±0.147;服药前后酶CYP2A6、XO的活性无显著性差异,酶NAT2的活性有显著性差异.结论银杏叶片可能不会影响其他经CYP2A6、XO酶代谢的药物临床疗效,但是可以影响与之合用经NAT2代谢的药物临床疗效.     

质子泵抑制剂对药物代谢酶CYP1A2、NAT2的影响分析

目的 以健康人群作为研究对象,从代谢表型探讨质子泵抑制剂与药物代谢酶CYP1A2、NAT2的关系.方法 以咖啡因作为药物代谢酶CYP1A2、NAT2的探针药物,用反相高效液相色谱(RP-HPLC)方法测定尿液中咖啡因代谢物.结果 健康人群CYP1A2酶活性指标呈对数正态分布,NAT2酶活性活性指标呈两态分布.结论 以咖啡因探针法测定正常人肝脏药物代谢酶CYP1A2、NAT2活性的RP-HPLC梯度洗脱直接进样法,为国内深入开展CYP1A2、NAT2代谢酶的研究开拓了一种新方法.     

泮托拉唑对人肝脏药物代谢酶CYP1A2、NAT2和XO活性影响的研究

目的:探讨泮托拉唑对人肝脏药物代谢酶CYP1A2、NAT2和XO活性的影响,预测泮托拉唑与常用药物的相互作用,指导临床医师合理用药。方法:以咖啡因作为药物代谢酶CYP1A2、NAT2和XO的探针药物,以反相高效液相梯度洗脱法测定30名受试者服用泮托拉唑前后人尿液内咖啡因5种主要代谢产物的相对含量,采用代谢物的比率分别评价人肝脏药物代谢酶CYP1A2、NAT2和XO活性的变化。结果:受试者用药前CYP1A2、NAT2和XO平均活性为3.37±1.22、0.50±0.09、0.49±0.09;服用泮托拉唑7 d后CYP1A2、NAT2和XO平均活性为3.50±1.23、0.48±0.12、0.48±0.13;服药前后3种酶活性没有显著性差异(P>0.05)。结论:泮托拉唑对人肝脏药物代谢酶CYP1A2、NAT2和XO活性无明显影响,泮托拉唑可能不会影响与之合用的需经CYP1A2、NAT2和XO代谢的药物临床疗效。     

藏药佐太对大鼠CYP1A2和NAT2活性的影响

目的:研究藏药佐太对大鼠细胞色素氧化酶(CYP1A2)、药物代谢酶N-乙酰基转移酶2(NAT2)活性的影响。方法:将70只SD大鼠随机均分为正常对照(生理盐水)组和佐太低、中、高剂量(1.2、3.8、12 mg/kg)单次给药组和多次给药组(每天1次,连续12 d),分别ig给药。正常对照组、佐太单次给药组于第2天,佐太多次给药组于第13天分别ig给予咖啡因(25 mg/kg),5 h后采集尿液,按10 mg/ml加入维生素C。采用高效液相色谱法测定大鼠尿液中咖啡因代谢物5-乙酰氨基-6-甲酰氨基-3-甲基尿酸(AFMU)、1-甲基黄嘌呤(1X)、1-甲基尿酸(1U)、1,7-二甲基尿酸(17U)的含量,以(AFMU+1X+1U)/17U、AFMU/(AFMU+1X+1U)比值来反映CYP1A2和NAT2活性。结果:与正常对照组比较,佐太中剂量单次给药组及多次给药组、高剂量多次给药组大鼠(AFMU+1X+1U)/17U、AFMU/(AFMU+1X+1U)比值降低,即CYP1A2和NAT2活性降低,差异有统计学意义(P<0.05)。结论:佐太对大鼠CYP1A2和NAT2活性有明显抑制作用。     

苦参对大鼠细胞色素P4501A2体内代谢活性的影响

目的以咖啡因作为探针药物,研究苦参对大鼠细胞色素P450 1A2(CYP1A2)体内代谢活性的影响。方法将Wistar大鼠随机分为4组:空白对照组、苦参组(实验组)、苯巴比妥组(诱导剂阳性对照组)和西咪替丁组(抑制剂阳性对照组)。苦参组,灌胃给予苦参溶液100 mg.kg-1;空白对照组,灌胃给予与苦参组体积相同的生理盐水;苯巴比妥组,腹腔注射苯巴比妥注射液50 mg.kg-1;西咪替丁组,每日腹腔注射西咪替丁注射液50 mg.kg-1,各组均为每日1次,连续5 d。第6 d,各组大鼠均经尾静脉注射咖啡因溶液2.5 mg.kg-1,于给药前及给药后不同时间,眼内眦静脉取血0.8 mL,用高效液相色谱法,测定血浆中咖啡因的浓度。结果给予大鼠苦参5 d后,苦参组的咖啡因AUC、MRT、Cmax明显低于空白对照组和西咪替丁组(P<0.05),明显高于苯巴比妥组(P<0.05);而CL明显高于空白对照组和西咪替丁组(P<0.05)而明显低于苯巴比妥组(P<0.05)。结论苦参可明显诱导大鼠CYP1A2的体内代谢活性;但诱导强度低于苯巴比妥。     

药物代谢酶细胞色素P4501A2的研究

细胞色素P4501A2是肝微粒体药物代谢酶家族的重要一员,它不但参与多种药物代谢,还在肿瘤的发生发展和治疗中起着重要的作用.本文简要综述了CYP4501A2的诱导剂、抑制剂、代谢底物、与疾病的关系及其研究进展.     

复方丹参滴丸对药物代谢酶CYP1A2，NAT2和XO活性影响的研究

目的 探讨复方丹参滴丸对CYP1A2,NAT2和XO活性的影响,指导临床医师合理用药。     

多环芳烃相关代谢酶CYP1A1和GSTP1基因多态性与不良孕产史的关系

目的 分析多环芳烃细胞色素P450 1A1(CYP1A1)、谷胱肽转移酶P1(GSTP1)代谢酶基因多态性与不良孕产史的关联。方法 回顾性研究2018年1月至2020年1月接诊的618例有不良孕产史的孕产妇，将其设为作为研究组，选定同期600例健康孕妇作为健康组，对比2组CYP1A1、GSTP1基因多态性，对比2组孕前体质量指数(BMI)、不良孕产史次数、是否服用叶酸、是否存在有害因素接触史、有无妊高症、妊娠糖尿病，Logistic回归分析不良孕产史传统影响因素与CYP1A1、GSTP1基因多态性的关系。结果 CYP1A1 MspI基因型GG比例研究组(80.26%)高于健康组(54.50%),CYP1A1 MspI基因频率分布2组比较，差异有统计学意义(P<0.05,95%CI:0.738～0.938)。研究组GSTP1 SnaBI基因型GG比例(52.43%)高于健康组(44.33%),2组GSTP1 MspI基因频率分布对比，差异有统计学意义(P<0.05),95%CI:0.744～0.928)。Logistic回归分析不良孕产史的独立危险因素是CYP1A1、GSTP...     

用咖啡因作探药,快速测定人体细胞色素P—450CYP1A2酶的活性

AIM: To develop a rapid HPLC method for the determination of cytochrome P-450 CYP1A2 activity. METHODS: A 300-microL plasma was prepared by extraction with 5-mL chloroform/isopropanol (9:1), and beta-hydroxyletheophylline was added as internal standard (IS). Samples were separated on an ODS column by a gradient elution system, of which mobile phase consisted of 0.05% acetic acid, acetonitrile, and methanol. The compounds of interest were monitored at 282 nm by UV detector. RESULTS: No potential interfering peaks were found. Paraxanthine (17X), IS and caffeine (137X) were rapidly eluted with baseline resolution, and their retention time was less than 13 min. The detection limits of both 17X and 137X were 0.1 mumol.L-1. Linear relations ranged over 1-100 mumol.L-1 and 1-200 mumol.L-1 with correlation coefficient of 0.9999 and 0.9987, respectively, for 17X and 137X. The coefficients of variation were within 6% for 17X, and 10% for 137X. The average recoveries for both compounds were ranged from 96% to 108%. CONCLUSION: This method is sensitive and rapid, and can be used for population studies of CYP1A2.     

HPLC直接进样测定咖啡因代谢物评价三种药物代谢酶活性

目的：建立测定尿中咖啡因的5种主要代谢物：5-乙酰氨基-6-甲酰氨基-3-甲基尿酸（AFMU）、1-甲基尿酸（1U）、1-甲基黄嘌呤（1X）、1，7-二甲基尿酸（17U）和1，7-二甲基黄嘌呤（17X）的高效液相色谱法，以评价N-乙酰基转移酶（NAT2）、细胞色素P450酶1A2（CYP1A2）和黄嘌呤氧化酶（XO）三种药物代谢酶的活性。方法：采用反相高效液相梯度洗脱法直接进样测定尿液内咖啡因代谢产物AFMU、1U、1X、17U和17X的相对含量，计算AFMU／（AFMU＋1X＋1U）、（AFMU＋1X＋1U）／17U和1U／（1X＋1U），绘制概率分布直方图，分别反映NAT2、CYP1A2和XO的活性。结果：NAT2活性呈两态分布，快、慢乙酰化代谢表型的临界点为0．26，CYP1A2和XO酶活性呈近似正态分布。结论：本方法简便、准确、快速，适合于尿中咖啡因代谢物的测定及NAT2、CYP1A2和XO等药物代谢酶活性的研究。     

银杏叶片溶出度研究

目的:探讨银杏叶片溶出度测定方法及溶出动力学,为评价和控制药品质量提供方法和参数.方法:采用转篮法,100 r·win-1,自身对照紫外分光光度法测定不同厂家银杏叶片在人工胃液和人工肠液中累积溶出百分率.并进行溶出动力学拟合,提取威布尔分布溶出参数进行统计学处理.结果:银杏叶片在人工胃液和人工肠液中溶出参数有所区别但无显著性差异(P>0.01),不同厂家的银杏叶片溶出参数有显著性差异(P<0.05).结论:建议在银杏叶片质量标准中增加溶出度项目;自身对照法做为银杏叶片体外溶出度测定方法操作简便可行.     

Regulation of Cytochrome P4501A Metabolism by Glutathione

Abstract: Gene expression of cytochrome P4501A (CYP1A) in the rainbow trout Oncorhynchus mykiss is dependent on aromatic hydrocarbon receptor signal transduction, and is markedly sensitive to tissue thiol status. Tissue glutathione (GSH) status was manipulated by exogenous GSH, L-buthionine-[S, R]-sulfoximine (BSO), lipoate or 1, 3-bis(2-chloroe-thyl)-1-nitrosourea (BCNU). Tissue GSH contents were significantly elevated in GSH- and lipoate-supplemented trout. Hepatic, renal and plasma GSH levels were markedly arrested in BSO-treated trout. Oxidized glutathione (oxidized GSH) levels were significantly elevated in the BCNU-supplemented group. Both BCNU treatment and BSO-induced GSH deficiency increased steady-state levels of hepatic CYP1A mRNA. Additional exposure to 0.1 mg/kg 3, 3′, 4, 4′-tetrachloro-biphenyl marginally suppressed the tetrachlorobiphenyl-dependent CYP1A induction in BSO-treated livers compared with the respective thiol treatment groups. Tetrachlorobiphenyl exposures altered efficiencies of thiol treatments and increased oxidized GSH content in all but the BSO-treated groups. However, exposure to 5 mg/kg tetrachlorobiphenyl altered effects of thiol treatments on CYP1A mRNA to a small extent, but catalytic activity of CYP1A was many times suppressed in BSO-treated and lipoate-supplemented fish. These results suggest that thiol status interferes with CYP1A metabolism in a two-way mode of action and provide further evidence for a cross-talk between cytochrome P4501A and glutathione.     

RP-HPLC法测定复方银杏叶片中葛根素的含量

目的:建立以RP-HPLC法测定复方银杏叶片中葛根素含量的方法。方法:色谱柱为Kromasil C18(250mm×4.6mm,5μm),流动相为甲醇-水(20∶80),流速为1mL.min-1,测定波长为250nm,柱温为35℃。结果:葛根素进样量在0.8~2.4μg范围内与峰面积积分值呈良好的线性关系(r=0.9993,n=5);平均回收率为99.98%,RSD=1.31%(n=5)。结论:本法简便、灵敏度高、重现性好,可用于复方银杏叶片的质量控制。     

银杏叶口崩片的制备和含量测定

目的：筛选银杏叶口崩片的制刺处方和成型工艺,建立银杏叶口崩片中总黄酮醇苷的高效液相色谱含量测定方法。方法：以口感、可压性、崩解时间为指标筛选处方,利用预混辅料制备口崩片。采用Elite Hypersil ODS2色谱柱（250 mm×4.6 mm,5μm）,以甲醇-0.4%磷酸溶液（50-50）为流动相,检测波长为360 nm;流速为1.0 ml·min-1,柱温为30℃,进样量为20μl。结果：经最佳制备工艺制得的银杏叶口崩片外观和口感良好,30 s内能完全崩解。在此色谱条件下,槲皮素在6.3563.50μg·ml-1范围内,线性关系良好（r=0.999 9）;山奈素在5.1351.25μg·ml-1范围内,线性关系良好（r=0.999 8）;异鼠李素在1.8518.50μg·ml-1范围内,线性关系良好（r=0.999 8）。槲皮素、山奈素、异鼠李素的平均回收率分别为97.84%、96.22%、95.55%,RSD分别为0.82%、1.03%、1.88%（n=5）。结论：银杏叶口崩片处方合理,制备工艺可行。建立的含量测定放法快速简便,准确可靠,重复性好,灵敏度高,专属性强,可用于银杏叶口崩片的质量控制。     

Cytochrome P4502E1 Inhibition by Propylene Glycol Prevents Acetaminophen (Paracetamol) Hepatotoxicity in Mice without Cytochrome P4501A2 Inhibition

Abstract: Acetaminophen hepatotoxicity is associated with its biotransformation to the reactive metabolite N-acetyl-p-benzoquinone imine that binds to protein. Two forms of cytochrome P450, CYP2E1 and CYP1A2, have been implicated as primarily responsible for the bioactivation. To determine the relative contributions of these P450's, overnight fasted male NMRI mice were pretreated with 10 ml of 50% v/w propylene glycol/kg or fluvoxamine (10 mg/kg) at–80 and–20 min. relative to acetaminophen dosing to inhibit CYP2E1 and CYP1A2, respectively. Mice were sacrificed at 0.5 or 4 hr after a hepatotoxic dose of acetaminophen (300 mg/kg). Propylene glycol or propylene glycol plus fluvoxamine, but not fluvoxamine alone protected against acetaminophen hepatotoxicity as indicated by abolished increase in serum alanine aminotransferase activity, less depletion of hepatic glutathione and lower livenbody weight ratios. Propylene glycol inhibited the activity of CYP2E1 as indicated by 84% reduction in the clearance of 3 mg/kg dose of chlorzoxazone, whereas fluvoxamine inhibited the activity of CYP1A2 as indicated by 40% reduction in the clearance of a 10 mg/kg dose of caffeine. For this animal model, the data are consistent with the notion that hepatotoxicity is associated with bioactivation of acetaminophen by CYP2E1 but not by CYP1A2.     

复方丹参滴丸对人N-乙酰基转移酶活性的影响

目的 探讨复方丹参滴丸对人N-乙酰基转移酶活性的影响,以便指导临床医师合理用药.方法 采用反相高效液相梯度洗脱法,测定服用复方丹参滴丸前后人尿液内咖啡因的3种主要代谢产物5-乙酰氨基-6-甲酰氨基-3-甲基尿酸(AFMU)、1-甲基尿酸(1U)和1-甲基黄嘌呤(1X)的相时含量,以AFMU/(AFMU 1X 1U)比率评价人N-乙酰基转移酶活性的变化.结果 受试者服药前N-乙酰基转移酶平均活性为0.36±0.12,服药14 d和28 d后平均活性为0.32±0.12和0.30±0.11,分别比服药前降低11.11%和16.67%,但并无统计学差异.结论 服用治疗剂量的复方丹参滴丸时N-乙酰基转移酶活性无明显影响,与需经N-乙酰基转移酶代谢的药物联用时.不影响其疗效.     

银杏叶片中槲皮素的示波极谱法测定

建立了示波檄谱法测定银杏叶片中槲皮素的含量。以25％盐酸水解银杏叶片样品，用1．5mol／L NH4OAc—NH4OH（pH8．0）为示波极谱底液，以K2CrO4为滴定剂，示波极谱图上CrO4^2-切口出现指示滴定终点。