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1.
目的 快速测定法莫替丁在人血浆中的浓度,并研究其药动学.方法 12名健康志愿者单剂量空腹po法莫替丁片40 mg,于给药后不同时间收集血浆样品,固相萃取,以阿莫西林为内标,采用液相色谱-质谱联用法测定法莫替丁在血浆中的浓度,并计算药动学参数.结果 在优化条件下,法莫替丁的线性范围是0.3~400 ng·mL~(-1) (r=0.9993),最低定量限为0.3 ng·mL~(-1),RSD=9.14%.法莫替丁片在所选受试者体内的动力学过程符合一室模型.T_(max)=2.63±0.36 h;C_(max)=150.52±6.09 ng·mL~(-1);AUC_(0~15)=764.54±87.56 μg·h·L~(-1);t_(1/2)=2.77±0.32 h.结论 所建方法灵敏度高、准确度好、专属性强,分析速度快,适用于法莫替丁血药浓度的测定及其药动学的研究.  相似文献   

2.
目的:研究复方醋酸曲安缩松乳膏在家兔体内药代动力学。方法:采用HPLC法测定6只单次外用醋酸曲安缩松乳膏家兔的药-时数值,以PKBP-NI程序拟合其药动学参数。结果:该药在家兔体内的转运过程符合具有滞后时间的一室模型特征,药动学参数如下:t_(max)为(3.9±0.3)h,C_(max)为(11.2±0.8)mg·L~(-1),t_(1/2)为(7.0±0.8)h,t_(lag)为(0.19±0.08)h,AUC为(176 ±22)mg·h·L~(-1)。  相似文献   

3.
目的研究两种厄贝沙坦氢氯噻嗪片在中国健康受试者体内的生物等效性。方法空腹试验和餐后试验各入组32例健康受试者,随机、开放、2周期、双交叉单剂量口服厄贝沙坦氢氯噻嗪片(150 mg/12.5 mg)受试制剂和参比制剂,采用液相色谱串联质谱(LC-MS/MS)法测定给药后不同时间点厄贝沙坦及氢氯噻嗪的血药浓度。采用Phoenix Win Nonlin 7.0软件计算药动学参数,考察两制剂生物等效性。结果空腹试验中受试制剂和参比制剂厄贝沙坦的药动学参数c_(max)分别为2 618.1和2 756.4 ng·mL~(-1),AUC_(0-t)分别为10 643.2和10 552.4 ng·h·mL~(-1),AUC_(0-∞)分别为11 126.7和11 000.4 ng·h·mL~(-1);氢氯噻嗪的药动学参数c_(max)分别为108.1和108.8 ng·mL~(-1),AUC_(0-t)分别为626.4和633.5 ng·h·mL~(-1),AUC_(0-∞)分别为649.6和651.3 ng·h·mL~(-1)。餐后试验中受试制剂和参比制剂厄贝沙坦的药动学参数c_(max)分别为2 712.3和2 823.1 ng·mL~(-1),AUC_(0-t)分别为9 887.2和10 006.7 ng·h·mL~(-1),AUC_(0-∞)分别为10 473.4和10 454.7 ng·h·mL~(-1);氢氯噻嗪的药动学参数c_(max)分别为79.3和85.1 ng·mL~(-1),AUC_(0-t)分别为601.2和624.6 ng·h·mL~(-1),AUC_(0-∞)分别为620.4和643.8 ng·h·mL~(-1)。受试制剂与参比制剂c_(max)、AUC_(0-t)和AUC_(0-∞)几何均数比值的90%置信区间均在87.23%~109.31%之间。结论两种厄贝沙坦氢氯噻嗪片在中国健康受试者体内具有生物等效性。  相似文献   

4.
目的 研究国产匹伐他汀钙片(降血脂药)在中国健康志愿者体内单次给药的药代动力学特征及安全性.方法 选择中国健康受试者12例,按3×3拉丁方设计,分别单次给予匹伐他汀钙片1,2,4 mg后,采用液相色谱-串联质谱联用法测定不同时间血中匹伐他汀的浓度,以DAS 2.0软件进行数据处理,求算药代动力学参数.结果 3个不同剂量组匹伐他汀的主要药代动力学参数:t_(1/2β)分别为(11.39±7.66),(10.00±7.30),(11.30±7.95)h;t_(max)分别为(0.83±0.29),(0.73±0.20),(0.85±0.46)h;C_(max)分别为(30.48±11.66),(60.80±22.97),(120.98±35.51)ng·mL~(-1);AUC_(0→72h)分别为(93.19±26.61),(179.46±52.86),(364.37±94.74)ng·mL~(-1)·h;AUC_(0→∞)分别为(96.70±27.42),(183.34±53.62),(372.86±95.84)ng·mL~(-1)·h;各剂量组的C_(max)、AuC_(0-72h)、AUC_(0→∞)随剂量的增加而成比例的增大,各组的K_(10)、t_(max)、t_(1/2β)、MRT_(0-72)、MRT_(0→∞)、CL/F、V/F等差异无统计意义.结论 口服给药剂量为1~4 mg时,匹伐他汀钙片在中国健康人体内具有线性药代动力学特征,其代谢特征基本与文献报道一致.  相似文献   

5.
目的:研究三黄汤煎剂中黄苓苷在大鼠体内的药动学规律。方法:大鼠ig三黄汤煎剂后,在规定时间取血,用高效液相色谱法测定血浆中黄芩苷浓度,并计算主要药动学参数结果:大鼠体内黄芩苷的主要药动学参数分别为t_(max1)=(15±4.23)min, t_(max2)=(6.8±0.54)h,C_(max1)=(4.49±1.56)μg·mL~(-1),C_(max2)=(3.25±1.23)μg·mL~(-1),AUC(0-18)=(35.52±12.35)μg·h·mL~(-1),t_(1-2)=(5.12±0.23)h,CL=(3.86±0.91)L·h~(-1)结论:该方法样品处理简单,快速准确,专属性好,灵敏度较高,可作为含黄芩苷中成药的血药浓度监测手段。  相似文献   

6.
盐酸氟西汀胶囊人体生物等效性研究   总被引:1,自引:0,他引:1  
目的:评价国产盐酸氟西汀胶囊与进口上市的盐酸氟西汀胶囊的人体生物等效性。方法:22例健康男性志愿者,随机分成2个序列,交叉单剂量口服40 mg 盐酸氟西汀胶囊,以液相色谱-质谱联用法测定血清样本中氟西汀的浓度,并计算相关药动学参数判定2种制剂是否生物等效。结果:测得盐酸氟西汀胶囊参比制剂和受试制剂中氟西汀的主要药代动力学数据t_(max)分别为(7.41±1.74)h和(7.36±1.87)h,C_(max)分别为(43.64±11.10)ng·mL~(-1)和(44.90±11.39)ng·mL~(-1),AUC_(0-)分别为(2817.7±927.5)ng·h·mL~(-1)和(2870.5±989.8)ng·h·mL~(-1),AUC_(0~∞)分别为(2847.4±952.9)ng·h·mL~(-1)和(2892.0±1012.0)ng·h·mL~(-1),t_(1/2(k_e))分别为(73.63±16.89)h 和(69.37±13.05)h,K_e 分别为(0.0099±0.0025)h~(-1)和(0.0104±0.0023)h~(-1)。国产盐酸氟西汀胶囊的相对生物利用度(101.74±12.44)%。结论:方差分析和双单侧 t 检验表明2种制剂生物等效。  相似文献   

7.
目的研究奥美拉唑对多西他赛在乳腺癌大鼠体内药动学的影响。方法采用7,12-二甲基苯并蒽建立大鼠乳腺癌模型。取18只乳腺癌大鼠随机分成单剂量组、多剂量组和对照组,每组6只。单剂量组灌胃给予奥美拉唑3.5 mg·kg~(-1),每日1次;多剂量组灌胃给予奥美拉唑3.5 mg·kg~(-1),每日2次;对照组每日灌胃给予相同体积生理盐水。持续给药7 d后,分别静脉注射多西他赛10 mg·kg~(-1)。并于给药前(0 min)和给药后1、5、10、20、30、60、120、240、480、600 min收集大鼠血浆。建立高效液相色谱-串联质谱(HPLC-MS/MS)法并测定大鼠血浆中多西他赛浓度,计算药动学参数。同时,考察奥美拉唑对多西他赛在肝微粒体中代谢的影响。结果对照组、奥美拉唑单剂量和多剂量组给药后,乳腺癌大鼠体内多西他赛的主要药动学参数c_(max)、AUC_(0-t)和t_(1/2)分别为(669.35±102.67)、(722.58±72.81)和(701.23±123.45)ng·mL~(-1);(2 010.63±307.23)、(2 487.61±252.43)和(2 875.86±317.55)ng·h·mL~(-1);1.74、2.28和3.01 h;与对照组相比,奥美拉唑单剂量组大鼠体内多西他赛的t_(1/2)显著升高(P<0.05),多剂量组AUC_(0-t)和t_(1/2)显著升高(P<0.05),但c_(max)无显著差异(P>0.05),而奥美拉唑单剂量和多剂量组间的药动学参数无显著差异(P>0.05)。在大鼠肝微粒体中,奥美拉唑可以非竞争性方式抑制多西他赛的代谢。结论奥美拉唑可提高多西他赛在乳腺癌大鼠体内的生物利用度,并减缓消除速率,可能会导致多西他赛药效及毒副作用的增加。  相似文献   

8.
目的研究比较在低氧和常氧条件下,常用抗生素罗红霉素在大鼠体内的药代动力学特征。方法建立快速高效的超高效液相质谱联用法,测定大鼠血浆中罗红霉素的浓度。SD大鼠灌胃给予罗红霉素(10 mg·kg~(-1)),测定不同时间点的大鼠血浆药物浓度,分别计算低氧与常氧大鼠的主要药代动力学参数,并进行统计分析。结果在1~1 000μg·L~(-1)浓度间,罗红霉素在血浆中有良好的线性关系,定量下限为1μg·L~(-1)。罗红霉素在常氧和低氧大鼠体内主要药动学参数分别为:AUC_(0-t)7 576μg·h·L~(-1)和3 761μg·h·L~(-1);MRT_(0-t)5.6 h和7.7 h;T_(1/2)3.4 h和3.9 h;t_(max)3.1h和3.4 h;C_(max)1 116μg·L~(-1)和372μg·L~(-1);CL 1.5和3.0 L·h~(-1)·kg~(-2)。与常氧大鼠药动学参数比较,低氧状态下罗红霉素在大鼠体内的药动学参数C_(max)和AUC均有明显降低。结论低氧条件下,罗红霉素在大鼠体内的体内暴露量明显降低,结果为罗红霉素在低氧状态下的给药方案优化和调整提供了重要的实验依据。  相似文献   

9.
目的:研究马来酸替加色罗片在中国健康受试者中的药代动力学特征。方法:采用LC-MS法研究单次和连续口服马来酸替加色罗片的药动学特征。结果:健康受试者分别单次口服6、12、18 mg马来酸替加色罗片后,药-时曲线符合二室开放模型,主要药代动力学参数t_(max)为(2.2±1.0)、(1.3±0.5)、(1.3±0.4)h;C_(max)为(3.4±0.4)、(8.5±1.4)、(12.0±2.4)ng/mL;t_(1/2α)为(5.5±6.4)、(4.6±5.6)、(2.0±2.0)h;t_(1/2β)为(16.2±2.4)、(15.2±1.8)、(14.9±2.0)h;AUC_(0→48)为(53±9)、(96±29)、(135±54)ng·h·mL~(-1);AUC_(0→∞)为(64±12)、(108±33)、(158±60)ng·h·mL~(-1);MRT为(16.3±1.0)、(14.8±1.1)、(14.6±0.7)h。C_(max)、AUC_(0→48)和AUC_(0→∞)在6~18 mg内与给药剂量呈线性关系。统计分析结果还表明t_(max)、t_(1/2α)、t_(1/2β)和MRT在上述不同剂量组间无统计学差异(P>0.05)。连续给药3 d后血药浓度达稳态,达到稳态后的t_(max)、C_(ss,max)、C_(ss,min)、C_(ss,avg)、DF值分别为(1.5±0.4)h、(8.1±1.3)、(2.6±0.7)、(4.4±0.8)ng/mL、(126±16)%。在相同剂量下,C_(max)、AUC_(0→48)、AUC_(0→∞)和t_(1/2β)等参数值较文献报道高。结论:在中国健康受试者中马来酸替加色罗片的体内过程符合二室开放模型,在6~18 mg范围内具有线性动力学特征。  相似文献   

10.
李飞娥  刘东  刘异  刘宇  周红华 《中国药师》2007,10(5):426-429
目的:研究单剂量和多剂量盐酸曲普利啶胶囊在中国健康志愿者体内的药物动力学特征。方法:健康受试者单次(2.5 mg)或多次(2.5 mg,tid,连续服药6d)口服盐酸曲普利啶胶囊,用LC-MS法测定血浆中曲普利啶浓度,用DAS 2.0处理数据。结果:本法线性良好,精密度、准确度、回收率均符合要求。所得药物动力学参数如下,单剂量:t_(1/2)=(5.88±1.62)h,t_(max)=(2.21±0.62)h,C_(max)=(27.50±6.32)ng·ml~(-1),AUC_(0-∞)=(216.74±67.18)h·ng·ml~(-1),MRT_(0-∞)=8.64±1.24 h。多剂量:t_(1/2)=(6.38±2.58)h,t_(max)=(1.71±0.58)h,AUC_(8S)=139.29±47.22 h·ng·ml~(-1),C_(max)=(27.78±6.52)ng·ml~(-1),C_(min)= (10.12±9.26)ng·ml~(-1),C_(av)=(17.41±5.90)ng·ml~(-1),DF=1.13±0.60。结论:该法灵敏度高,操作简便,盐酸曲普利啶胶囊多剂量给药与单剂量给药的药物动力学参数基本一致,无蓄积,给药后安全性良好。  相似文献   

11.
Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (cmax, tmax, AUC) were calculated for plasma and tissue time courses. The mean AUCtissue /AUCplasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - tmax Time to peak concentration - cmax Peak concentration  相似文献   

12.
In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.  相似文献   

13.
1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.  相似文献   

14.
本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。  相似文献   

15.
Polymorphisms in genes involved in neurotransmission in relation to smoking   总被引:4,自引:0,他引:4  
Smoking behavior is influenced by both genetic and environmental factors. The genetic contribution to smoking behavior is at least as great as its contribution to alcoholism. Much progress has been achieved in genomic research related to cigarette-smoking within recent years. Linkage studies indicate that there are several loci linked to smoking, and candidate genes that are related to neurotransmission have been examined. Possible associated genes include cytochrome P450 subfamily polypeptide 6 (CYP2A6), dopamine D1, D2, and D4 receptors, dopamine transporter, and serotonin transporter genes. There are other important candidate genes but studies evaluating the link with smoking have not been reported. These include genes encoding the dopamine D3 and D5 receptors, serotonin receptors, tyrosine hydroxylase, trytophan 2,3-dioxygenase, opioid receptors, and cannabinoid receptors. Since smoking-related factors are extremely complex, studies of diverse populations and of many aspects of smoking behavior including initiation, maintenance, cessation, relapse, and influence of environmental factors are needed to identify smoking-associated genes. We now review genetic polymorphisms reported to be involved in neurotransmission in relation to smoking.  相似文献   

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1.?Pradigastat is a potent and specific diacylglycerol acyltransferase-1 (DGAT1) inhibitor effective in lowering postprandial triglycerides (TG) in healthy human subjects and fasting TG in familial chylomicronemia syndrome (FCS) patients.

2.?Here we present the results of human oral absorption, metabolism and excretion (AME), intravenous pharmacokinetic (PK), and in vitro studies which together provide an overall understanding of the disposition of pradigastat in humans.

3.?In human in vitro systems, pradigastat is metabolized slowly to a stable acyl glucuronide (M18.4), catalyzed mainly by UDP-glucuronosyltransferases (UGT) 1A1, UGT1A3 and UGT2B7. M18.4 was observed at very low levels in human plasma.

4.?In the human AME study, pradigastat was recovered in the feces as parent drug, confounding the assessment of pradigastat absorption and the important routes of elimination. However, considering pradigastat exposure after oral and intravenous dosing, this data suggests that pradigastat was completely bioavailable in the radiolabeled AME study and therefore completely absorbed.

5.?Pradigastat is eliminated very slowly into the feces, presumably via the bile. Renal excretion is negligible. Oxidative metabolism is minimal. The extent to which pradigastat is eliminated via metabolism to M18.4 could not be established from these studies due to the inherent instability of glucuronides in the gastrointestinal tract.  相似文献   

19.
Diclofop-methyl (DM) is a chlorophenoxy derivative used in large quantities for the control of annual grasses in grain and vegetable crops. In this study, the genotoxic effects of DM were investigated by measuring chromosomal aberrations (CAs) in mouse bone-marrow cells and CA and the comet assay in human peripheral lymphocytes. Mice were treated with 15.63, 31.25, 62.5, and 125?mg/kg body weight of DM intraperitoneally for 24 hours, and 15.63-, 31.25-, 62.5-, 125-, and 250-µg/mL concentrations were applied to human lymphocytes for both 24 and 48 hours. In in vivo treatments, DM significantly, but not dose dependently, increased the total chromosome aberrations, compared to both negative and solvent controls. Cell proliferation was significantly, but not dose dependently, affected by all doses. In in vitro treatments, DM (except 15.63 µg/mL) significantly and dose dependently increased the frequency of chromosome aberrations. Also, 250 µg/mL of 48-hour treatment was found to be toxic. Cell proliferation was significantly and dose dependently affected by DM applications, when compared to negative control. In in vitro treatments, DM significantly decreased the mitotic index only at the highest concentration for 24 hours, and 62.5- and 125-µg/mL concentrations for 48 hours. In the comet assay, a significant and dose-dependent increase in comet-tail intensity was observed at 62.5-, 125-, and 250-µg/mL concentrations. The mean comet-tail length was significantly increased in all concentrations. Our results demonstrate that DM is genotoxic in mammalian cells in vivo and in vitro.  相似文献   

20.
Based on blood and cerebrospinal fluid samples collected in a full-term neonate, the penetration of tramadol in the central nervous system is described. Following intravenous administration of tramadol, a lag time of about 4 h was observed until full blood–brain equilibration was achieved. This pharmacokinetic observation is in line with a recent pharmacodynamic evaluation of the central opioid effects of tramadol in adults.  相似文献   

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