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81.
复方盐酸二甲双胍片在人体内药物动力学和生物等效性研究 总被引:1,自引:0,他引:1
目的 建立人血浆中盐酸二甲双胍的反相离子对高效液相色谱和格列本脲的液相色谱-质谱测定方法,研究复方盐酸二甲双胍片(盐酸二甲双胍250mg/格列本脲1.25mg×2片)相对于联合使用的盐酸二甲双胍片(500mg)和格列本脲片(2.5mg)在男性健康志愿者体内的药物动力学行为,评价其生物利用度和生物等效性。方法 采用双交叉随机实验设计:20名受试者交叉口服复方盐酸二甲双胍片2片或口服盐酸二甲双胍片与格列本脲片各1片,服药后于0.5、1.0、1.5、2.0、2.5、3.0、3.5、4.0、5.0、6.0、8.0、12、24、36h分别取血,分离血浆,分别依法测定盐酸二甲双胍和格列本脲的血药浓度。结果 测得口服复方盐酸二甲双胍片或联合使用盐酸二甲双胍片与格列本脲片后,盐酸二甲双胍的达峰时间分别为(2.0±0.7)h和(2.1±0.9)h,峰浓度分别为(1402.4±349.2)μg·L-1和(1329.7±315.4)μg·L-1,消除半衰期分别为(3.84±0.61)h和(4.26±0.96)h,AUC0-24分别为(7292.7±1967.5)μg·L-1和(7416.2±1843.9)μg·h·L-1;格列本脲的达峰时间分别为(3.1±0.9)h 和(3.0±0.8)h,峰浓度(71.7±22.7)μg·L-1和(70.3±20.7)μg·L-1,消除半衰期分别为(5.05±2.01)h 和(4.78±1.64)h,AUC0-24分别为(367.6±168.7)μg·L-1和(352.6±144.7)μg·h·L-1;以联合服用等剂量的盐酸二甲双胍片与格列本脲片为参比,以AUC0-24计算得复方盐酸二甲双胍片之盐酸二甲双胍和格列本脲的相对生物利用度,分别为101.1%±28.5%和123.7%±82.9%。结论 建立的分析方法准确灵敏,测得数据可靠。统计学分析表明复方盐酸二甲双胍片与联合使用盐酸二甲双胍片和格列本脲片显生物等效。 相似文献
82.
菟丝子中槲皮素药代动力学研究 总被引:1,自引:0,他引:1
目的建立菟丝子中槲皮素的含量测定方法,研究槲皮素体内动力学规律.方法建立快速敏感的高效液相色谱-紫外检测法(HPLC-UV),以卡马西平为内标,以菟丝子灌胃给药后,大鼠含药血清样品经液-液萃取后在C18反相色谱柱上进行分离测定.结果槲皮素血药浓度在0.05~9μg/mL浓度范围内线性关系良好(r=0.9998).方法回收率为86.65~99.07%,提取回收率为79.91~84.56%,最低检测限为0.05μg/mL.结论槲皮素在大鼠体内的动力学过程表现为具吸收的二室开放模型,其中t1/2(Ab)=0.13h,t1/2(α)=0.19h,t1/2(β)=1.22h,tmax=0.333h.实验结果可为菟丝子在临床用药的安全性和有效性提供依据. 相似文献
83.
GC-MS法研究麻黄汤中麻黄碱、伪麻黄碱的人体内过程 总被引:13,自引:0,他引:13
目的建立用于同时测定麻黄碱( ephedrine, E)、伪麻黄碱( pseudoephedrine, PE)血药浓度的气相色谱-质谱法( GC-MS),并探讨二者在人体内的药代动力学.方法用 GC-MS法测定人血药浓度,所得数据用 WinNonlin4.0.1药代动力学程序处理,求出有关参数.结果 E、 PE分别在 5~ 1000 ng/mL, 2.5~ 500 ng/mL的范围内线性关系良好(R2=0.9985,r2=0.9994) ,加样回收率分别为 107.5 %~ 96.2 % , 102.5 %~ 93.9 %.两者日内、日间精密度的RSD < 5 %,血浆样品 60 d内稳定,符合生物样本分析要求.结论该方法稳定、准确,灵敏度高,适于 E、 PE的血药浓度测定. 相似文献
84.
L. J. C. van Warmerdam Geert-Jan Creemers S. Rodenhuis Hilde Rosing Maureen de Boer-Dennert Jan H. M. Schellens W. W. ten Bokkel Huinink Brian E. Davies Robert A. A. Maes Jaap Verweij Jos H. Beijnen 《Cancer chemotherapy and pharmacology》1996,38(3):254-260
Topotecan is a novel semisynthetic derivative of the anticancer agent camptothecin and inhibits the intranuclear enzyme topoisomerase
I. The lactone structure of topotecan, which is in equilibrium with the inactive ring-opened hydroxy acid, is essential for
this activity. We performed a pharmacokinetics study as part of phase II clinical trials in patients with various types of
solid tumors, giving topotecan at 1.5 mg/m2 per day by 30-min infusion for 5 consecutive days, with courses being repeated every 3 weeks. Previously validated limited-sampling
models, using concentration measurements in samples obtained 2 h after infusion, were used to calculate the area under the
plasma concentration-time curves (AUCs) for both chemical forms. Samples were obtained from a total of 36 patients over 136
treatment days. The mean AUC of the closed-ring form (AUCclosed) was 8.74 (range 2.3–16.3) μM min per day, and the mean AUC of the ring-opened form (AUCopen) was 11.5 (range 3.2–46.0) μM min per day (interpatient variability 34–61%). In each patient the AUC values achieved on the 1st day of administration were
similar to and, thus, predictive for those achieved during the following days, with a day-to-day variation of 7.39% being
recorded for the AUCclosed and that of 12.6%, for the AUCopen. There was no drug accumulation during the 5 consecutive treatment days of each cycle. However, despite the large interpatient
pharmacokinetic variability, the importance of regular drug monitoring on this schedule can be questioned, as the pharmacodynamic
variability was relatively small.
Received: 15 June 1995/Accepted: 19 October 1995 相似文献
85.
86.
紫杉醇冻干纳米乳在大鼠体内的药动学 总被引:2,自引:0,他引:2
目的:研究紫杉醇冻干纳米乳在大鼠体内的药动学特征。方法:建立测定大鼠血浆中紫杉醇的HPLC-紫外检测法,大鼠股静脉注射给药后于不同时间点进行后眼眶静脉丛穿刺取血,测定其血浆中的血药浓度,并用3P97药动学程序对血药浓度进行处理。结果:紫杉醇可与血浆中的其它成分较好地分离,在0.12~60μg/mL的血药浓度范围内呈良好的线性关系。紫杉醇注射液和冻干纳米乳两种制剂大鼠静脉给药后体内药动学符合二室模型.后者AUC和MRT均大于前者.结论:紫杉醇纳米乳可延长药物在大鼠体内的循环时间。 相似文献
87.
Quantification of rhynchophylline in rabbit plasma by UPLC-MS/MS and its application in a pharmacokinetic study 下载免费PDF全文
It was recently revealed thatRhynchophylline (Rhy), an important constituent of Uncaria rhynchophylla, possessed antihypertensive and neuroprotective effects. However, no information about the pharmacokinetics of Rhy in a herbivorous speciessuch as rabbit is available. Allometric scaling is valuable in designing human pharmacokinetic parameters from preclinical species. To investigate the characteristics of Rhy in vivo, a rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the measurement of Rhy concentrations in rabbit plasma. The method was linear over the concentration range of 0.01–10.24 µg/mL. Intra-day and inter-day precision and accuracy were less than 8.0%. The recoveries were in the range of 94.17%–103.32%. Matrix effects (ME) were minor. After oral administration of Rhy at 20, 40 and 80 mg/kg, the mean elimination half-life (t1/2) for these doses were 1.19, 1.49 and 1.37 h in rabbits, respectively. There was a proportionate increase in the maximum concentration (Cmax) and the area under the blood concentration-time curve (AUC∞) for three doses. The developed method was suitable for the study on pharmacokinetics of Rhy after oral administration and it may provide a valuable basis for clinical application of such a bioactive compound of herbal medicines. 相似文献
88.
目的:建立高效液相色谱-质谱/质谱联用法(HPLC-MS/MS)测定血浆中牡荆素的方法,并用于大鼠药动学研究。方法:采用Capcell Pak C18柱(50 mm×2.0 mm,I.D.,5μm),柱温25℃,流动相为甲醇∶水(95∶5,0.1%甲酸),流速为0.2 mL/min。用负离子电喷雾电离源,多反应方式检测,选择监测的离子反应为m/z 431~311(牡荆素)和m/z 269~225(大黄素,内标)。结果:牡荆素在0.5~2 000 ng/mL线性关系良好,相关系数为0.9960,最低定量限为0.5 ng/mL。加样回收率76.1%~89.0%,日内日间精密度RSD均小于11%。结论:该方法分析速度快、操作简单、灵敏度高,可用于大鼠血浆中牡荆素的浓度测定及药动学研究。 相似文献
89.
Nygren P Hande K Petty KJ Fedgchin M van Dyck K Majumdar A Panebianco D de Smet M Ahmed T Murphy MG Gottesdiener KM Cocquyt V van Belle S 《Cancer chemotherapy and pharmacology》2005,55(6):609-616
Background Aprepitant is a selective neurokinin-1 receptor antagonist that is effective for the prevention of nausea and vomiting caused by highly emetogenic chemotherapy. In vitro, aprepitant is a moderate inhibitor of the CYP3A4 enzyme, which is involved in the clearance of several chemotherapeutic agents. In this study we examined the potential for aprepitant to affect the pharmacokinetics and toxicity of intravenously administered docetaxel, a chemotherapeutic agent that is primarily metabolized by CYP3A4.Methods A total of 11 cancer patients (4 male, 7 female, aged 50–68 years) were enrolled in this multicenter, randomized, open-label, two-period, crossover study. Patients received a single infusion of docetaxel monotherapy, 60–100 mg/m2, on two occasions at least 3 weeks apart. During one of the cycles (treatment A), patients received docetaxel alone. During the alternate cycle (treatment B), they also received aprepitant 125 mg orally 1 h prior to docetaxel infusion (day 1), and a single oral dose of aprepitant 80 mg on days 2 and 3. The pharmacokinetic profile of docetaxel was assessed over 30 h following docetaxel infusion. Blood counts were monitored on days 1, 4, 7, and 14.Results Ten patients completed the study. Concomitant administration of aprepitant did not cause any statistically or clinically significant changes in docetaxel pharmacokinetics. Values for docetaxel alone (treatment A) versus docetaxel with aprepitant (treatment B) were as follows: geometric mean AUC0–last was 3.26 vs 3.17 g h/ml (P>0.25; ratio B/A 0.97); geometric mean AUC0– 3.51 vs 3.39 g h/ml (P>0.25; ratio B/A 0.96); geometric mean Cmax was 3.53 vs 3.37 g/ml (P>0.25; ratio B/A 0.95); and geometric mean plasma clearance was 23.3 vs 24.2 l/h/m2 (P>0.25; ratio B/A 1.04). The corresponding harmonic mean half-life values were 10.1 and 8.5 h. The two treatment regimens had similar tolerability profiles; the median absolute neutrophil count nadirs were 681/mm3 during treatment with docetaxel alone and 975/mm3 during aprepitant coadministration.Conclusions Aprepitant had no clinically significant effect on either the pharmacokinetics or toxicity of standard doses of docetaxel in cancer patients. Aprepitant at clinically recommended doses may have a low potential to affect the pharmacokinetics of intravenous chemotherapeutic agents metabolized by CYP3A4. 相似文献
90.
目的研究洛铂和顺铂在小鼠血浆、肾脏和肿瘤内的药物浓度随时间变化的规律,为放疗增敏提供实验数据。方法 70只C57BL/6近交系Lewis肺癌荷瘤小鼠随机分组,按10mg药物/kg体重经尾静脉分别给小鼠注射药物(洛铂或顺铂),给药后在0.5、2、4、24、48、72、96 h分别将小鼠处死获取血液和组织标本(肿瘤和肾脏),应用ICP-MS方法测定标本铂含量。结果洛铂和顺铂的血浆药时曲线均符合三室模型,半衰期分别为51.139h和35.583h,洛铂在血浆中的清除速率大于顺铂[0.532L/(h.kg)对0.192 L/(h·kg)];洛铂和顺铂在肿瘤组织的浓度均在给药后迅速达到最大[(2.79±0.35)μg/g对(4.78±1.11)μg/g],然后迅速下降,在4 h后分别降至0.99±0.21μg/g和3.39±0.55μg/g,在96 h肿瘤中仍有药物存在,浓度分别为0.23±0.05μg/g和1.41±0.71μg/g。肿瘤药物浓度与血浆药物浓度呈对数相关,Rsq分别为0.948和0.837。结论洛铂和顺铂在小鼠体内静脉给药后半衰期长,肿瘤内药物浓度在给药后很快达到最大,在4 h降至平台期,96 h仍有药物存在,顺铂在肿瘤内的浓度高于洛铂;洛铂在小鼠体内的清除速率快于顺铂;可以通过检测血浆中的洛铂和顺铂浓度来估算肿瘤内的药物浓度。 相似文献