单次口服兰索拉唑的药代动力学研究

兰索拉唑(Lansoprazole)是新型的质子泵抑制剂。在体内以其代谢物AG-1812和AG-2000形式与壁细胞膜上的H~ -K~ -ATP酶非竞争性结合,从而作用于胃酸分泌的终末通道。由于在结构上与奥关拉唑不同,抑制胃酸分泌作用更强,对消化性溃疡的愈合、反流性食管炎的缓解,较其它抑制胃酸药物的作用更为迅速。本研究应用高压液相色谱法测定6名男性健康志愿者一次口服兰索拉唑的血药浓度,以便了解该药在我国健康人体内的药代动力学规律。     

兰索拉唑在消化性溃疡病人中的药代动力学研究

目的在消化性溃疡病人中观察兰索拉唑的药代动力学的变化，进一步了解该药的代谢规律。方法选取经胃镜检查确诊为消化性溃疡的患者为试验组（Ｇ组，ｎ＝６）及健康志愿者为对照组（Ｃ组，ｎ＝６），口服兰索拉唑胶囊３０ｍｇ，定时取血通过高压液相方法测定血药浓度。利用３Ｐ８７药代动力学程序模拟药时曲线，计算药代动力学参数。结果兰索拉唑符合一房室模型。试验组中，５位患者的吸收速率常数Ｋα较对照组的Ｋα明显增加，吸收半衰期Ｔ１２α及达峰时间Ｔｍａｘ明显减少。血药浓度高峰Ｃｍａｘ有明显提高。而清除速率常数Ｋβ、清除半衰期Ｔ１２β也有较明显的差别，其表观分布容积Ｖ／Ｆ、清除率ＣＬ／Ｆ及血药浓度曲线下面积ＡＵＣ差别均不显著。１位幽门不全梗阻患者的药代动力学曲线表明吸收明显延迟。结论兰索拉唑口服后，分布广泛，代谢迅速。消化性溃疡患者应用时，其吸收速率和其排泄明显加快。血药浓度高峰明显增加，对于治疗该病可能具有重要的意义。     

单剂量静脉滴注兰索拉唑在中国健康人体的药代动力学

目的 研究中国健康志愿者单次静脉滴注兰索拉唑(抑胃酸药)的药代动力学特点.方法 12名健康志愿者,先后单次静滴3个剂量(15,30,60 mg)兰索拉唑;用高效液相色谱-紫外检测法测定给药后不同时间点的血药浓度,用3P97软件计算药代动力学参数.结果 血药浓度-时间曲线符合二房室模型,健康受试者单次静滴3个剂量(15,30,60 mg)兰索拉唑后主要的药代动力学参数:C_(max)分别为(1105.65±506.24),(2171.33±799.02),(4070.53±643.04)μg·L~(-1);t_(1/2)分别为(1.63±0.86),(2.30±2.01),(1.90±1.19)h;AUC_(0-12)分别为(991.16±814.49),(3495.87±1770.92),(8351.14±2599.90)μg·h·L~(-1).结论 兰索拉唑的体内过程在男女性别间无显著差异,剂量在15～60 mg内较安全.     

兰索拉唑片在人体内的药动学研究

目的 采用RP-HPLC法进行兰索拉唑的血药浓度检测和药动学研究.方法 采用Agilent C18色谱柱(250 mm×5mm,5μm),流动相为乙腈-1‰三乙胺水溶液(pH7) (30∶70),流速1.0 mL·min-1,进样量20 μL,内标为奥美拉唑.血浆样品经乙酸乙酯提取后,于285 nm处检测.结果 0.05～1.60 μg· mL-1兰索拉唑与峰面积比值的线性关系良好(r ＝0.9997),最低定量限为20 ng·mL-1(S/N ＞3),日内RSD＜ 7.94％(n＝5),日间RSD ＜9.41％(n＝5),提取回收率＞95.79％.结论 所用方法可用于临床上兰索拉唑片血药浓度的检测及药动学研究.     

兰索拉唑在正常及溃疡模型家兔体内药代动力学研究

目的:建立高效液相色谱法分析兔血浆中兰索拉唑的含量,并比较兰索拉唑在正常及溃疡模型家兔体内药代动力学行为的差异。方法:家兔于20℃水中浸泡8小时建立胃溃疡模型,耳缘静脉给予兰索拉唑注射剂后,分别在不同时间点收集血样,HPLC法测定,采用DASS2.0软件计算给药后的药物动力学参数。结果:兰索拉唑浓度在20~2000 ng.mL-1范围内线性关系良好,最低检测浓度为20 ng.mL-1。低、中、高3个浓度的提取回收率均大于85%,批内、批间相对标准差低于10%。与正常兔比较,溃疡模型家兔给予兰索拉唑药物后体内AUC(0-6.5)明显增加[(916.84±338.61)vs(522.72±172.16)μg.h.L-1,P<0.05]、体内平均滞留时间延长MRT(0-6.5)[(0.824±0.203)vs(0.69±0.13)h,P<0.05]、血浆消除半衰期增大[(0.88±0.44)vs(0.53±0.28)h,P<0.05]、血浆清除率显著减小[(2.74±1.70)vs(6.23±2.21)L.h-1,P<0.05]、最大血药浓度增大[(1091.31±348.94)vs(682.20±234.56)μ...     

兰索拉唑血药浓度的HPLC测定

采用反相ＨＰＬＣ法测定了６例健康志愿者口服兰索拉唑３０ｍｇ后的血药浓度。实验标本用乙醚－二氯甲烷（７：３）萃取，以对＝羟基苯甲酸乙酯为内标物，使用Ｃ１８柱分离，流动相为水－惭腈－＝正辛胺，流速１．０ｍｌ／ｍｉｎ，外皮长２８５ｎｍ，线性范围０．１－２．０μｇ／ｍｌ，最低检测浓度为５０ｎｇ／ｍｌ，日内ＲＳＤ平均为１．１％，日间ＲＳＤ平均为４．７％。     

高效液相色谱法测定人血浆中兰索拉唑浓度

目的建立测定人血浆中兰索拉唑浓度的高效液相色谱方法。方法血浆样品经二氯甲烷和乙醚的混合提取液提取后,以乙腈:0.05mol/L磷酸二氢氨溶液(pH7.0,35:65)为流动相,经PAPCELLPAK-C18色谱柱分离,于285nm波长处检测。结果兰索拉唑浓度在0.025～2.0μg/mL范围内线性关系良好,最低检测浓度为0.025μg/mL;低、中、高3个浓度的提取回收率均大于74%,日内、日间相对标准差低于8.22%。结论本方法准确、快速,可满足临床药代动力学研究的要求。     

兰索拉唑

兰索拉唑是一种有效的酸泵抑制剂，作用于胃壁细胞分泌道最后的酶催骤，减少胃酸的分泌。少于８周的临床试验结果表明，用该药治疗十二指肠溃疡，４周时的愈合速率和总愈合 率均明显优于安慰剂和雷尼替丁，也比法莫替丁的愈合速率快。兰索拉唑３０ｍｇ／ｄ治疗胃溃和反流性食管炎，８周后的愈合率为８５％－９５％，治疗反流性食管炎的疗效优于雷尼替丁，而与奥美拉唑相似；缓解反流症状比雷尼替丁或奥美拉唑快得多。初步资料表明，     

兰索拉唑有关物质测定方法改进

目的改进兰索拉唑有关物质的测定方法.方法参照英国药典,采用十八烷基硅烷键合硅胶柱测定兰索拉唑有关物质.结果与结论采用十八烷基硅烷键合硅胶柱和采用氨基键合硅胶柱,可达到基本相同的分离效果,使色谱柱选择性增加.     

某院门急诊注射用兰索拉唑合理用药调查分析

目的了解本院注射用兰索拉唑在门急诊应用的合理性。方法从HIS系统中调出本院2013年7月-2013年9月应用注射用兰索拉唑的电子处方,依据说明书,对注射用兰索拉唑的适应证、用法用量等进行合理性分析。结果共调出处方64张,存在不合理用药处方41张,不合格率64．1％。结论本院门急诊注射用兰索拉唑存在严重不合理应用情况,医院应加强管理,以提高注射用兰索拉唑使用的合理性。     

Effects of lansoprazole on pharmacokinetics and metabolism of theophylline

The effect of the new substituted benzimidazole proton pump inhibitor, lansoprazole, on pharmacokinetics and metabolism of theophylline has been studied in healthy adults given oral lansoprazole 30 mg once daily for 11 days. On Days 4 and 11 of 300 mg aminophylline was simultaneously administered orally and blood samples for theophylline analysis were taken over 24 h. Urine samples were collected for up to 24 h and were assayed for theophylline and its major metabolites 1,3-dimethyluric acid (1,3-DMU), 1-methyluric acid (1-MU) and 3-methylxanthine (3-MX). The pharmacokinetic parameters of theophylline were determined, and the urinary recovery of unchanged theophylline and its major metabolites were calculated.After administration of lansoprazole for 4 days, no significant alteration in the terminal elimination half-life (t _1/2) or the mean residence time (MRT) was detected. However, there was a significant decrease of about 13% in the area under the plasma concentration-time curve (AUC) and a significant increase of about 19% in the apparent clearance (CL_app). Lansoprazole treatment for 11 days caused a significant decrease of approximately 12% in t _1/2 and about 10% in the MRT of theophylline, although neither AUC nor CL_app showed a significant alteration. The excretion of 3-MX in the urine was significantly increased by about 20% after lansoprazole treatment for 4 and 11 days, although there was no significant alteration in the excretion of unchanged theophylline, 1,3-DMU or 1-MU.The results indicate that repeated administration of lansoprazole to humans induces the hepatic microsomal P-450-dependent drug oxidation system that mediates N-1-demethylation of theophylline, consequently increasing its metabolism.     

我院住院患者注射用兰索拉唑合理用药点评分析

注射用兰索拉唑在我院化疗辅助药中使用频繁,主要为减轻放、化疗产生的恶心、呕吐等副反应,防止因重大手术导致应激性溃疡。随机抽查2015年10月~2016年3月应用兰索拉唑住院患者200例,发现不合理用药48例,其中无适应证用药9例（4.5%）,给药途径不适宜39例（19.5%）。表明注射用兰索拉唑用药合理性有待加强。     

兰索拉唑肠溶片人体生物利用度及生物等效性研究

目的:研究兰索拉唑肠溶片人体生物利用度及生物等效性。方法:22例健康志愿受试者交叉口服兰索拉唑肠溶片和兰索拉唑胶囊剂各30 mg,以非那西丁为内标,HPLC-UV法测定血浆中兰索拉唑浓度。结果与结论:健康志愿者口服两种制剂各30 mg后,Cm ax分别为(1 057.26±230.42)ng.mL-1和(1 336.35±288.88)ng.mL-1;tm ax分别为(2.6±0.6)h和(2.1±0.6)h;t1/2分别为(1.85±0.28)h和(1.75±0.34)h;AUC0-12分别为(3 565.34±1 233.03)h.ng.mL-1和(3 951.22±1 375.82)h.ng.mL-1。各参数经统计学配对t检验,均无显著性差异(P>0.05)。兰索拉唑肠溶片与兰索拉唑胶囊剂在健康志愿者体内的药动学参数相似。     

注射用兰索拉唑细菌内毒素检查法的可行性研究

目的对注射用兰索拉唑进行干扰试验,建立注射用兰索拉唑细菌内毒素检查的试验方法。方法采用《中国药典》2010年版二部附录细菌内毒素检查法进行试验。结果将注射用兰索拉唑稀释至浓度为50μg/ml时,对细菌内毒素检查法无干扰作用。结论应用鲎试剂进行注射用兰索拉唑细菌内毒素检查是可行的。     

Genetic polymorphism of CYP2C19 and lansoprazole pharmacokinetics in Japanese subjects

Objective: We investigated whether interindividual differences in the pharmacokinetic disposition of lansoprazole are attributed to the genetic polymorphism of CYP2C19 which occurred by two mutations, CYP2C19m1 and CYP2C19m2, in 20 Japanese subjects. Methods: Polymerase chain reaction (PCR) restriction fragment length polymorphism procedures were used to detect the CYP2C19m1 mutation in exon 5 and the CYP2C19m2 mutation in exon 4 using SmaI and BamHI, respectively. Results: Ten subjects were homozygous (wt/wt subjects) for the wt allele in both exon 5 and exon 4, four subjects were heterozygous (wt/m1) for the CYP2C19m1 mutation, and two subjects were heterozygous (wt/m2) for the CYP2C19m2. The remaining four subjects had both mutated alleles in CYP2C19 genes, i.e., two were homozygous (m1/m1) for the defect in exon 5 and two were heterozygous (m1/m2) for the two defects in exons 5 and 4. The subjects in group 1 (wt/wt, wt/m1 and wt/m2) were the extensive metabolizers (EMs) for 5-hydroxylation of lansoprazole and were in the range of hydroxylation indexes from 3.83 to 19.8, whereas the subjects in group 2 (m1/m1 and m1/m2) were the poor metabolizers (PMs) and the indexes were in the range of 38.5 to 47.6. In group 2, AUC, t_1/2 and CL/f of lansoprazole were significantly greater, longer, and lower, respectively, than those in group 1. Conclusion: The hydroxylation of lansoprazole to 5-hydroxylansoprazole was apparently impaired in the subjects with the genetic defects of CYP2C19 (m1/m1 or m1/m2). Received: 12 November 1996 / Accepted in revised form: 18 February 1997     

氟罗沙星片剂,胶囊剂的人体药物动力学和相对生物利用度研究

9名男性健康自愿受试者采用三交叉单剂口服国产氛罗沙星片剂、胶囊和进口氟罗沙星片剂各400mg的药代动力学参数比较。血、尿药浓度用HPLC检测．结果表明：体内过程符合一室模型，主要药代动力学参数分别为：AUC：82.30±14．30、81．13±8．45与83．92±14.27h·mg／L；Cmax：4．71±0．83、4．67±0．51与4．86±0．89mg／L；Tmax：1．88±0．44、1．90±0．39与1．92±0．23h；T1／2ke：11．02±0．96、10．93±0．68与10．86±0．82h；V／F（c）：79．08±13．31、78.42±8．70与76．39±12．93L；Cl／F：5．00±0．98、4．98±0．52与4．88±0．73L／h。服药48h的尿中原型药排出率分别为给药量的57．4％，55．9％和60．7％。国产氧罗沙星片剂和胶囊口服后药物动力学参数与进口片剂相仿．其相对生物利用及分别为98.07％与96．68％。     

兰索拉唑关键中间体的合成工艺改进

目的改进兰索拉唑关键中间体的合成方法.方法通过改变文献合成过程中所用溶剂,单独用氢氧化钠的水溶液为溶剂,减少了环境污染,同时提高了产物的收率及操作的安全性.结果及结论新合成方法可使收率稳定在98%以上,高于文献报道的方法,降低了成本,更适合工业化的要求.