合用盐酸黄连素前后环孢素A的人体药动学

目的 :研究健康受试者合用盐酸黄连素 (berberinehydrochloride ,Ber)前后环孢素A(cyclosporinA ,CsA)的动力学过程 ,以分析两药相互作用发生的部位。方法 :6名健康男性志愿者在单剂口服CsA 3mg·kg-1后开始连续服用Ber 30 0mg ,bid× 10d ,最后一次与单剂CsA 3mg·kg 　 -1同时口服。每次口服CsA后即按时采血 ,用FPIA法测定全血CsA浓度 ,并计算出药动学参数。结果 :在健康志愿者合用Ber后 ,CsA的AUC值增加 19.6 % ,差异具非常显著性 (P <0 .0 1)。结论 :推测Ber对CsA的影响部位可能主要在肠道 ,Ber可能增加CsA的吸收或减少肠代谢。     

盐酸黄连素对肾移植受者环孢素A增效作用的临床药代动力学研究

目的研究盐酸黄连素对肾移植受者使用环孢素A增效作用的体内动力学过程.方法选择肾移植术后1个月以内、连续服用环孢素A 2周、肝肾功能稳定的患者6名,环孢素A剂量6mg.kg-1·d-1,用FPIA方法(单抗)检测合用黄连素前后各时间点环孢素A全血浓度.结果单服环孢素A的主要药代动力学参数分别为tmax(h)1.33±0.52,Cmax(μg·L-1)1224.75±296 20,Cmin(μg·L-1)173.95±78.71,t1/2(h)2.62±1.00,AUC μg·h·L-14681.34±1300.45,CL/F(L·h-1)35±15;与黄连素合用的主要药代动力学参数为tmax(h)3.00±1.26,Cmax(μg·L-1)1050.10±290.86,Cmin(μg·L-1)321.31±161.29,t1/2(h)5.33±2.60,AUCμg·h·L-16265.71±1 871.33,CL/F(L·     

合用盐酸小檗碱对环孢素A人体药动学的影响

目的:研究合用盐酸小檗碱(Ber)对肾移植受者和健康受试者环孢素A(CsA)药动学的影响,以分析两药相互作用发生的部位.方法:采用自身对照的方法,12例健康受试者和6例肾移植术后1个月的患者在个体CsA剂量不变的前提下,改变给药途径、两药同时或分开服用和改变合用频率等条件,按时间点采集血样,用FPIA法测定全血CsA浓度,并计算出药动学参数.结果:肾移植受者合用Ber和CsA后,CsA的AUC平均增加(34.5±17.8)%;口服6mg·kg-1CsA和Ber 0.3g,bid,末次两药分开服用的健康受试者平均AUC没有增加;口服3mg·kg-1CsA和Ber 0.3g,bid,末次两药同时服用的健康受试者平均AUC增加(19.2±10.4)%;静注3mg·kg-1CsA和口服Ber 0.3g,bid的健康受试者平均AUC减少(16.0±7.2)%.结论:两药必须同时服用方可发生相互作用,只有两药均在肠道时,CsA的吸收才会增加,提示肠道可能是Ber影响CsA吸收的作用部位之一,Ber可能增加CsA的吸收或减少肠代谢.Ber与CsA同时口服可增加CsA的生物利用度.     

单剂量吗丁啉对环孢素A药动学参数的影响

本文研究同服吗丁啉（Ｄｏｍｐｅｒｉｄｏｎｅ）对６例肾移植初期病人口服环孢素Ａ药物动力学过程的影响，荧光偏振免疫法多抗试剂测定环孢素Ａ全血浓度，ＰＫＢＰ－Ｎ１药物动力学程序计算单服环孢素Ａ及环孢素Ａ与吗丁啉同服的药物动力学参数，ｔ检验比较两组主要动力学参数。研究结果表明：同服１０ｍｇ吗丁啉对环孢素Ａ口服吸收动力学无显著影响（Ｐ＞０．０５）。     

环孢素A血药浓度的监测与药动学研究

环孢素（Ａ（Ｃｙｃｌｏｓｐｏｒｉｎ Ａ，ＣｓＡ）是目前用于器官移植中预防排斥反应和治疗自身免疫性疾病的最好的免疫抑制药物。可用于骨髓、肝脏、心脏和肾脏移植的排异反应，对于预防胰、角膜、心、移植后的排异反应也获成功。对某些生疾病也有效，在我国已膛渐开始使用。由于它具有较大的肾生，药动学参数个体差异较大，因此世界多数器官移植中心认为在环孢素Ａ治疗中血药浓度的监测和药动学研究，对预防移植器排异反应和减少     

肾移植受者环孢素A与盐酸小檗碱合用的临床研究

目的研究盐酸小檗碱与环孢素A长期联合应用增加肾移植受者环抱素A血浓度的作用。方法52名服用环抱素A+盐酸小檗碱患者为试验组,52名单服环抱素A患者为对照组,以环抱素A全血浓度及肝、肾功能生化检测指标作为临床评价指标。结果合用盐酸小檗碱患者环抱素A全血浓度与合用前比较增幅达75%,与对照组比较有显著性提高（P<0.001）。盐酸小檗碱与环抱素A合用对肝、肾功能无明显影响。结论盐酸小檗碱能明显升高肾移植受者环抱素A血浓度。在升高环抱素A血浓度的同时,盐酸小檗碱并不增加环抱素A的毒性反应。盐酸小檗碱与环抱素A合用可减少环抱素A用药量,节省环抱素A费用。     

环孢素A人体药动学影响因素分析

环孢素Ａ(ｃｙｃｌｏｓｐｏｒｉｎＡ ,ＣｓＡ)是一种高效免疫抑制剂 ,具有亲脂性的环状多肽结构 ,含 11个氨基酸。该药于 1971年从真菌Ｔｏｌｙｐｏｃｌａｄｉｕｍｉｎｆｌａｔｕｍ中分离出来 ,1978年首次用于临床 ,现广泛用于肾脏、肝脏、心脏、骨髓移植患者及自身免疫性疾病的治疗。ＣｓＡ可选择性地抑制Ｔ辅助淋巴细胞及免疫反应 ,主要作用于淋巴细胞增殖早期 ,抑制作用是可逆的。ＣｓＡ不抑制造血系统 ,也不直接作用于巨噬细胞 ,因而不引起白细胞和血小板减少。ＣｓＡ的主要不良反应为与剂量有关的肾毒性、肝毒性等。由于ＣｓＡ的生物利…     

联苯双酯对环孢素A经大鼠小肠给药药动学影响的研究

目的:阐明联苯双酯(bifendate,BFD)对环孢素A(cyclosporin,CsA)经大鼠小肠给药药动学的影响。方法:两组大鼠分别给予0.5%CMC-Na和BFD(20mg.kg-1)连续灌胃6d,第7天分别从十二指肠幽门端注入CsA(1mg.kg-1)或CsA(1mg.kg-1) BFD(20mg.kg-1),从门静脉采血,用荧光偏振免疫法测定全血CsA浓度。结果:与单用CsA组相比,联用BFD组的Cmax平均降低55.7%(P<0.01),AUC平均降低49.7%(P<0.01)。联用BFD组的t1/2β、CL/F、V/F与单用CsA组相比明显升高(P<0.01或0.05)。其余参数在两组间差异无显著性(P>0.05)。结论:BFD可明显降低CsA的生物利用度,肠道可能是此相互作用发生的部位之一。     

环孢素A在健康人体内的药物动力学

目的:测定环孢素A(CsA)在健康人体的药物动力学参数.方法:10名健康志愿者单剂量po CsA 150mg后,固相萃取HPLC法测定其血药浓度,所得数据采用3P87程序拟合,求出有关药物动力学参数.结果:C_(max)=(815.35±210.72)ng/ml,t_(max)=(1.36±0.25)h,T_(1/2a)=(0.98±0.20)h,T_(1/2p)=(6·82±1.30)h.结论:CsA在健康人体内呈二房室开放模型分布,药物动力学参数个体差异大.     

环孢素A与盐酸小檗碱合用对大鼠肝脏和小肠药物代谢酶的影响

目的:研究盐酸小檗碱(berberine chloride,Ber)与环孢素A(CsA)合用对大鼠肝脏和小肠药物代谢酶的影响.方法:采用分光光度法测定各给药组大鼠肝脏和小肠微粒体中红霉素N-脱甲基酶(ERD)、氨基比林N-脱甲基酶(ADM)和谷胱甘肽转移酶(GST)的活性.结果:Ber组和Ber CsA组能明显抑制肝微粒体中ERD、ADM和GST酶活性(P< 0.05 ),而且Ber CsA组较CsA单用组有更明显的抑制作用(P< 0.05 ).Ber CsA组还能明显抑制肠微粒体中ERD、ADM和GST酶活性(P< 0.05 ).结论:Ber与CsA合用时,能显著抑制大鼠肝脏和小肠药物代谢酶活性,这可能是Ber增加CsA血药浓度的一个重要机制.     

Pharmacokinetics of oral cyclosporin a (Sandimmun) in healthy subjects

Summary Extensive pharmacokinetic (PK) profiles after oral dosing of 300 mg cyclosporin A (CsA) were determined in whole blood by radioimmunoassay (RIA) in 14 healthy male volunteers, using two-compartment models with either first order (M1) or zero order (M0) absorption. According to zero order absorption the mean of the following PK parameters was determined: terminal half-life=12.1±5.0 h, apparent volume of distribution at steady-state=5.6 ±2.1 l · kg^–1, apparent clearance=0.51±0.11 l · h^–1 · kg^–1. The time lag between drug ingestion and first blood level was short, 0.38±0.11 h. Drug absorption lasted for 2.8±1.6 h. The end of absorption was indicated in each individual by a sharp drop in blood levels.The observations support the assumption that CsA is absorbed in the upper part of the small intestine with a clear-cut termination (absorption window). This assumption may explain the high degree of variability in the bioavailability of CsA.This work was presented in abstract form at the British Pharmacological Society Meeting in Bath, UK, 9th–11th April 1986     

头孢吡肟注射液在汉族健康人体的药物代谢动力学

目的研究汉族健康志愿者单剂量静脉滴注盐酸头孢吡肟后的药物代谢动力学。方法汉族健康志愿者10名,男女各半,单剂量静脉滴注盐酸头孢吡肟1.0 g,采用HPLC法测定血浆中头孢吡肟的含量,用DAS软件进行数据处理。结果健康志愿者单剂量静脉滴注1.0 g盐酸头孢吡肟后的药物动力学参数:mρax为(68.75±10.41)mg.L-1、t1/2β为(1.97±0.20)h、AUC0-10.5 h为(136.89±23.02)mg.h.L-1、AUC0-∞为(139.69±23.78)mg.h.L-1。结论汉族健康志愿者单剂量静脉滴注盐酸头孢吡肟的体内药物动力学过程符合二室模型,不同性别受试者药物动力学参数的差异无统计学意义。     

Pharmacokinetics of nicardipine enantiomers in healthy young volunteers

Objectives: The present study was conducted to compare pharmacokinetic behaviors of nicardipine enantiomers given in different doses with different formulations of racemic nicardipine in healthy volunteers. Methods: One or two 20-mg racemic nicardipine tablets, and a 40-mg sustained-release capsule of nicardipine were administered to eight healthy volunteers in a cross-over fashion and pharmacokinetic parameters were evaluated. Enantiomer concentrations were determined by GC-MS combined with chiral stationary phase HPLC. Results and conclusions: Serum concentration of (+)-nicardipine was approximately 2–3 times higher than that of (−)-nicardipine in 20- and 40-mg doses of conventional formulations and a non-linear increase in bioavailability with dose was demonstrated. The value for AUC of (+)-nicardipine was approximately 2.3–2.8 times greater than that of the (−)-nicardipine (P < 0.05) when 20 and 40 mg racemic nicardipine were administered in a conventional preparation. Relative bioavailability of the sustained-release preparation vs the conventional preparation was 28% and 44% for (+)- and (−)-nicardipine, respectively, for the 40-mg dose. Received: 23 September 1996 / Accepted in revised form: 23 February 1997     

Pharmacokinetics of (+)-rolipram and (−)-rolipram in healthy volunteers

Summary Plasma levels of S-(+)-rolipram and R-(–)-rolipram in six healthy male volunteers were measured by radioimmunoassay after intravenous injection of 0.1 mg and oral administration of 1.0 mg of the pure enantionmers. Following i.v. treatment, plasma levels of both isomers declined in three phases, with half-lives of 0.2 h, 0.6–0.9 h and 6–8 h. Total clearance was 6 ml · min^–1 · kg^–1. Oral administration of 1.0 mg gave a peak concentration of 16 ng · ml^–1 after 0.5 h. Bioavailability of (+)-rolipram was 77% and of the (–) enantiomer it was 74%. There was no significant difference in C_max, half-life, total clearance or bioavailability between the two enantiomers.     

替格瑞洛在中国健康男性志愿者中的药动学及药效学研究

目的：研究替格瑞洛在中国健康志愿者中药动学及药效学,为其临床合理使用提供依据。方法：选14名健康男性志愿者,分别单次口服替格瑞洛180 mg,在不同时间点采集血样分别用于药动力学及药效学研究,其中药动学采样时间点为给药前、给药后0.5,1,1.5,2,3,4,5,6,8,12,16,24,36,48 h,药效学采样时间点为给药前他和给药后1,2,4,12,24,48 h,药动学血浆样品采用蛋白沉淀法处理,超高效液相色谱-串联质谱（UPLC-MS/MS）法测定原药、活性代谢产物浓度;药效学采用四通道血小板聚集仪测定ADP诱导的血小板聚集率,以血小板聚集抑制的变化程度作为替格瑞洛的药效学指标。用WinNonlin软件处理所得数据。结果：14例健康受试者口服180 mg替格瑞洛后,替格瑞洛原药、活性代谢产物AR-C124910XX在人体内平均t_max分别为（1.9±0.6）h和（2.1±0.6）h,平均t_1/2分别为（8.3±1.1）h和（9.7±2.5）h,平均C_max分别为（1 447.0±532.2）ng·mL^-1和（384.5±90.2）ng·mL^-1,平均AUC_0-last为（9 023.0±3 285.4）ng·mL^-1·h和（3 445.0±723.2）ng·mL^-1·h,平均AUC_0-∞为（9 208.7±3 437.6）ng·mL^-1·h和（3 594.4±827.0）ng·mL^-1·h。替格瑞洛对血小板抑制的达峰时间为4 h,对血小板抑制的最大效应E_max为（75.9±11.9%）。替格瑞洛的抗血小板效应随替格瑞洛及AR-C124910XX降低而减弱。结论：本研究系统考察了14例健康志愿者服用替格瑞洛后的药动学及药效学,为临床使用替格瑞洛剂量调整、优化治疗方案提供了理论依据。     

Pharmacokinetics of S-adenosyl-L-methionine in healthy volunteers

Summary S-Adenosyl-L-methionine (AdoMet) kinetics was studied in 6 male subjects given 100 and 500 mg i. v. Drug concentrations in plasma and urine were assayed using a radioenzymatic method. Pharmacokinetic parameters were estimated according to an open two-compartment model. The apparent volumes of distribution after the 100 and 500 mg doses were 407±27 and 443±36 ml/kg (mean±SEM), terminal half-lives 81±8 and 101±7 min and body clearances 3.7±0.5 and 3.1±0.2 ml/min per kg. Urinary excretion was 34±3 and 40±2% of the administered dose. The results demonstrate that drug disposition occurs more via metabolism than via renal excretion, and it is not dependent on the administered dose. Binding of AdoMet to serum proteins is negligible.     

来氟米特在中国健康人群中的群体药动学研究

目的：建立来氟米特口服给药在中国健康受试者体内的群体药动学模型,探讨其药动学特征及可能的影响因素。方法：21名健康男性受试者参与本次研究,应用Phoenix NLME（Vision 8.0）软件中的群体模块分析来氟米特口服给药后其代谢产物的血药浓度数据,估算相关药动学参数及其变异情况。结果：来氟米特活性代谢产物特立氟胺在健康志愿者中符合一级吸收的一室模型。吸收速率常数K_a、分布容积V、药物清除率CL的群体典型值分别为0.691 h^-1、12.843 L和0.031 L·h^-1。协变量筛选结果显示,BMI对分布容积V有显著影响（P<0.01）。结论：本研究成功建立了来氟米特在中国健康人群中的群体药动学模型,最终模型可对个体药代参数做出精确的估计,BMI对分布容积V有显著影响。     

Pharmacokinetics and absolute bioavailability of salbutamol in healthy adult volunteers

Summary Salbutamol was administered to sixteen healthy male volunteers intravenously and by mouth in liquid, tablet, and capsule form using a Latin-Squares design. Pharmacokinetic parameters from intravenous data were similar to previously reported values obtained with oral administration, with a mean terminal half-life of 3.8 h and a mean clearance of 439 ml·min⁻¹·1.73 m⁻². Peak plasma concentrations of 10–20 ng·ml⁻¹ were obtained 1–3 h following oral administration. The absolute bioavailability of each of the oral preparations was 44%. While statistically significant differences in lag time and time to peak concentration were noted among the various oral preparations, the drug is rapidly absorbed in all three dosage forms and the observed differences are unlikely to be of clinical significance.