尼莫地平自微乳化液大鼠小肠吸收动力学研究

以测定尼莫地平含量为指标，采用大鼠在体小肠吸收实验方法，对尼莫地平自微乳化液大鼠小肠吸收动力学进行了研究。实验表明：尼莫地平自微乳化液大鼠小肠吸收较好，循环灌流3h后．胆管结扎的大鼠小肠药物吸收百分率为84．74％，胆管未结扎的大鼠小肠药物吸收百分率为81．54％，胆管结扎与不结扎对吸收率无显著影响。     

尼莫地平大鼠在体肠吸收动力学

目的研究尼莫地平在大鼠各肠段的吸收动力学特征。方法采用大鼠在体肠段灌流实验 ,主要从吸收部位、药物浓度、pH值等 3方面对尼莫地平的肠段吸收特性进行研究。结果尼莫地平在大鼠肠道内无特定吸收部位 ,各肠段吸收速率常数按十二指肠、空肠、结肠、回肠顺序依次下降 ,吸收速率常数分别为 0 0 6 87、0 0 6 2 0、0 0 5 97、0 0 4 89h-1。在 4 8～ 14 3μmol·L-1浓度内药物吸收量与浓度呈线性关系 ;在 pH 5 0～ 7 4内药物吸收不受 pH值影响。 结论尼莫地平在大鼠全肠段均有吸收 ,吸收符合一级动力学特征 ,吸收机制为被动扩散 ,适于制备日服 1次缓释给药系统     

来曲唑在大鼠体内药代动力学的性别差异(英文)

目的:研究来曲唑(Letr)药动学性别差异性。方法:ig Letr 2mg/kg后,测定在雄、雌性大鼠血浆、组织中浓度及粪、尿中回收率。结果:ig Letr 6 h以后,雄鼠中血药浓度显著低于雌鼠,如给药24,36,48和72h,雌鼠血药浓度分别为雄鼠的3.3,5.6,10.5和7.4倍。雄鼠AUC也仅为雌鼠的1/3,其半衰期分别为10.5和40.4h。120h内,雌鼠尿和粪中排泄分数分别为5.78％±1.40％和6.61％±1.10％,而雄鼠仅分别为1.30％±0.59％和0.87％±0.31％;给药后24h,雌鼠组织中药物浓度显著高于雄鼠。结论:Letr在大鼠体内的药动学存在较大的性别差异。     

尼莫地平片的相对生物利用度及药物动力学研究

目的　对尼莫地平片相对生物利用度及药物动力学进行研究。方法　采用反相高效液相色谱法 (RP HPLC)测定 10名志愿受试者单剂量口服 12 0mg尼莫地平片供试品与标准参比制剂后 ,尼莫地平血药浓度的变化。用 3p87药动学程序处理实验数据 ,并对实验结果进行配对t检验和双单侧t检验。结果　药时曲线下面积分别为 82 .5 1± 2 8.73ng·ml-1·h与 82 .92± 30 .93ng·ml-1·h ,达峰时间分别为 1.75± 0 .2 6h与 1.70± 0 .2 6h ,峰浓度分别为 2 8.84± 9.0 5ng·ml-1与 2 9.0 5± 8.6 9ng·ml-1。结果表明二者AUC、峰浓度及达峰时间无显著性差异 ,尼莫地平片供试品的相对生物利用度为 10 0 .70 %± 7.4 4 %。结论　尼莫地平片供试品与标准参比制剂为生物等效制剂。     

口服国产尼莫地平胶囊在健康人体的药代动力学研究

目的 :探讨国产尼莫地平胶囊在健康人体的药代动力学。方法 :用高效液相色谱法测定12名男性健康志愿者口服尼莫地平胶囊后的血药浓度 ;用3p97软件计算有关药代动力学参数。结果 :该制剂的T1/2β(h)、Tmax、Cmax、AUC0～6 分别为 (2 53±1 18)h、(0 42±0 14)h、(75 41±27 65)ng/ml、(155 85±49 54)ng/(h·ml) ,药 -时曲线符合二室开放模型。结论 :该制剂在体内滞留时间短 ,于0 4h左右达血药浓度峰值 ,其测定数据可为临床用药提供参考。     

尼莫地平片相对生物利用度及药物动力学研究

本实验采用反相高效液相色谱法测定10名志愿受试者单剂量口服120mg尼莫地平片供试品与标准参比制剂后,尼莫地平血药浓度变化情况,经3p87药动学程序处理,药时曲线下面积分别是:82.51±28.73ng/ml×h与82.92±30.93ng/ml×h,达峰时间分别为:1.75±0.26h与1.70±0.26h,峰浓度分别是:28.84±9.05ng/ml与29.05±8.69ng/ml. 配对t检验与双单侧t检验结果表明:二者药时曲线下面积、峰浓度及达峰时间均无显著性差异,尼莫地平片供试品与标准参比制剂为生物等效制剂.尼莫地平片供试品的相对生物利用度为:100.70%±7.44%.     

尼莫地平对卡马西平的药物动力学影响

采用荧光偏振免疫分析法(FPLA),按自身对照法在六只家兔身上对卡马西平单用及与尼莫地平合用中卡马西平浓度变化进行观测.结果表明,合用尼莫地平后卡马西平药物动力学模型稍有改变.而单用与合用卡马西平后,其半衰期(T1/2)、药时曲线下面积(AUC)、消除率(CL)、表观分布容积(Vd)、峰浓度(Cmax)差异无统计学意义(P＞0.05).     

法莫替丁大鼠在体小肠吸收动力学研究

应用大鼠在体肠吸收实验方法研究了法莫替丁各肠段的吸收动力学特征。实验表明 :法莫替丁在肠道各部位的吸收速率按十二指肠、空肠、回肠、结肠顺序下降 ,吸收速率常数分别为0 0 5 0 8,0 0 44 6 ,0 0 415 ,0 0 2 87h-1。药物在肠道内的吸收呈现一级吸收动力学过程 ,其吸收机制为被动扩散     

尼莫地平片剂人体药代动力学及生物利用度

报告１０名男性健康志愿受试者随机交叉口服尼莫地平试验片和参比片各１２０ｍｇ的药代动力学和相对生物利用度．试验片和参比片Ｃｍａｘ分别为（３９１．８４±１４７．５２）和（３６８．９７±１７３．６６）μｇ／Ｌ，Ｔｍａｘ分别为（０．５５±０．１８）和（０．６４±０．２９）ｈ，ＡＬＬＣ分别为（７９０．８３±２０６．９６）和（７８４．０３±１９３．４３）μｇ／Ｌ·ｈ．统计学检验二者无显著性差异（Ｐ＞０．０５）．试验片的人体相对生物利用度为１０１．５０％±１４．００％，变异系数为１３．７０％．     

Gender differences in pharmacokinetics of oral warfarin in rats

Gender different pharmacokinetics of warfarin were investigated after oral administration at a dose of 2 mg/kg to male and female rats. The concentrations of warfarin in rat plasma were analysed by the HPLC method. Noncompartmental analysis was used for the calculation of the total area under the plasma concentration-time curve from time zero to time infinity (AUC) and terminal half-life of warfarin. After oral administration of warfarin to female rats, the AUC was significantly greater (345 compared with 180 microg h/ml) than that in male rats.     

Gender differences in the hepatic elimination and pharmacokinetics of lobeglitazone in rats

The pharmacokinetics of lobeglitazone (LB) was studied after intravenous administration at a dose of 1 mg/kg and oral administration at doses of 0.1, 1 and 10 mg/kg in male and female rats. The area under the plasma concentration–time curve from time zero to infinity (AUC_inf) after intravenous administration was approximately 7.1 times higher in female rats than in male rats. In addition, the AUC_inf in the case of oral administration was at least 4.4 times higher in female rats and appeared to increase in proportion to the dose in both genders. The in vitro half‐lives were 18.8 ± 4.45 min and 60.7 ± 11.2 min, as evidenced by incubating liver microsomes obtained from male and female rats, respectively. As a result, the estimated CL_int for LB for male rat liver microsomes (0.0779 ± 0.0233 ml/min/mg protein) was much higher than that for female rat liver microsomes (0.0233 ± 0.0039 ml/min/mg protein, p < 0.05). These observations suggest that there are gender differences in the pharmacokinetics and hepatic metabolism for LB in rats. Copyright © 2015 John Wiley & Sons, Ltd.     

Gender differences in ondansetron pharmacokinetics in rats

It has been reported that ondansetron is primarily metabolized via hepatic CYP2D and 3A1/2 in male Sprague-Dawley rats, and CYP2D1 and 3A2 are male dominant and male specific isozymes, respectively, in rats. Thus, it could be expected that the pharmacokinetics of ondansetron would be changed in male rats compared with those in female rats. Thus, gender-different ondansetron pharmacokinetics were evaluated after its intravenous or oral administration at a dose of 8 mg/kg to male and female Sprague-Dawley rats. After intravenous administration of ondansetron to male rats, the AUC and time-averaged non-renal clearance (Clnr) of the drug were significantly smaller (22.6% decrease) and faster (27.3% increase), respectively, than those in female rats. This probably could be due to faster hepatic blood flow rate in male rats. After oral administration of ondansetron to male rats, the AUC of the drug was also significantly smaller (58.8% decrease) than that in female rats, and this could have been due mainly to increased intestinal metabolism of ondansetron in addition to increased hepatic metabolism of the drug in male rats.     

五味子乙素在大鼠体内药代动力学的性别差异

目的研究五味子乙素在不同性别大鼠体内药代动力学的差异。方法雌、雄大鼠均灌胃给药（100mg／kg）后,测定五味子乙素的血药浓度。结果雌性大鼠体内的血药浓度显著高于雄性大鼠,生物利用度比雄性大鼠高约3倍,消除半衰期比雄性大鼠长。结论五味子乙素在不同性别的大鼠体内药代动力学特征具有明显差异。     

肾移植受者口服环孢素A药代动力学的性别差异

目的 :研究性别差异对肾移植受者口服环孢素A(CsA)的药代动力学影响。方法 :选择肾移植术后 2wk肝肾功能稳定的患者 41名 ,男 2 1名 ,女 2 0名。口服环孢素剂量 6mg·kg- 1·d- 1,用FPIA方法检测各时间点CsA全血浓度并用 3p87药动学程序拟合CsA药动学参数。结果 :男性和女性口服CsA的主要药动学参数分别为 :tmax(h) :2 .9± 1 .0和 2 .2± 0 .9,Cmax(mg·L- 1) :1 .0± 0 .4和 0 .9± 0 .5 ,Cmin(mg·L- 1) :0 .2 0± 0 .0 9和 0 .1 7± 0 .1 1 ,T1 2 (a) (h) :0 .8±0 .6和 0 .7± 0 .5 ,T1 2 (e) (h) :3 .0± 1 .2和 2 .8±0 .8,AUC0 - 12 (mg·L- 1·h- 1) :5.5± 1 .4和 4 .5± 1 .7,CL F(L·h- 1) :40± 2 5和 47± 35 ,V F(C) (L) :1 59±1 0 8和 1 72± 92。结论 :肾移植患者口服CsA的AUC0 - 12 和tmax具有性别差异     

阿霉素对去甲斑蝥素在大鼠体内药动学的影响

目的研究大鼠静脉给予阿霉素（ADM）对去甲斑蝥素（NCTD）体内药物动力学的影响。方法用HPLC-MS方法测定ADM和NCTD合并给药与NCTD单独给药大鼠血浆中的NCTD浓度,比较两者的药动学参数。结果ADM和NCTD合并给药组与NCTD单独给药组相比在分布速度常数（α）、分布相半衰期（t1/2α）、中央室向周边室的转运速度常数（k12）3个药动学参数有统计学差异（P〈0.05）,其余药动学参数之间无显著差异（P〉0.05）。结论NCTD与ADM合用时,ADM不会显著影响NCTD在大鼠体内的药动学过程,两药合用增效的原因主要在于药效学上的协同作用。     

Gender differences in pharmacokinetics of lumefantrine and its metabolite desbutyl-lumefantrine in rats

Lumefantrine has been reported to be mainly bio-transformed by cytochrome P450 isozyme 3A4 to desbutyl-lumefantrine (DLF) in human liver microsomes. Since CYP3A is expressed in a sex specific manner in rats, it could be expected that the pharmacokinetics of lumefantrine would be changed in male rats compared with those in female rats. The pharmacokinetics of lumefantrine and its active metabolite DLF were evaluated after intravenous (0.5 mg/kg) and oral (20 mg/kg) administration of lumefantrine to male and female Sprague-Dawley rats. The quantitative bioanalysis was carried out by the liquid chromatography tandem mass spectrometry method. After intravenous and oral administration of lumefantrine the area under the curve (AUC) of lumefantrine was significantly higher in female rats than that in male rats, whereas the AUC of DLF was significantly lower in female rats in comparison with male rats. This lower AUC of DLF in female rats could have been due to reduced metabolism of lumefantrine in female rats. The bioavailability (%F) of lumefantrine was 1.66 times higher in male rats than that in female rats.     

乳糖酸红霉素对葛根素药物动力学的影响

目的研究葛根素在大鼠体内的药物动力学过程以及乳糖酸红霉素对葛根素在大鼠体内药物动力学过程的影响。方法对大鼠分别单独静注葛根素溶液 ,联合静注葛根素和不同剂量的乳糖酸红霉素溶液 ;采用高效液相色谱法测定葛根素在大鼠体内的血药浓度 ;用 3P97药动学程序计算其药物动力学参数。结果葛根素在大鼠体内的药物动力学过程呈双隔室开放模型 ;乳糖酸红霉素在低剂量时 (0 2 5g·L-1和 2 5 0g·L-1)对葛根素的药动学过程无显著性影响 (P >0 0 5 ) ,但在高剂量时 (12 5 0 g·L-1)有显著性影响 (P <0 0 1)。结论葛根素与乳糖酸红霉素合用时 ,乳糖酸在一定质量浓度内 ,二者可联合用药 ;在较高质量浓度 (12 5 0g·L-1)时会显著抑制葛根素从大鼠体内的消除 ;二者合并用药时应对葛根素进行临床给药监测