乌苯美司胶囊人体药代动力学和生物等效性试验

目的:采用HPLC-MS/MS法研究乌苯美司胶囊在人体的药代动力学,并评价生物等效性。方法:24例健康男性受试者单次交叉口服30 mg乌苯美司胶囊受试制剂和参比制剂,测定给药后不同时间点血浆中乌苯美司经时血药浓度,采用DAS 2.0软件进行药代动力学参数计算和生物等效性评价。结果:受试者单次口服试验制剂与参比制剂后,达峰时间分别为(0.72±0.28)和(0.80±0.15)h;峰浓度分别为(2 416.83±379.56)和(2 291.57±418.92)μg.L-1;AUC0～t分别为(3 950.66±589.84)和(4 012.93±521.49)μg.L-1.h;AUC0～∞分别为(3 957.04±590.19)和(4 016.23±520.60)μg.L-1.h;t1/2分别为(3.49±1.91)和(2.80±1.51)h。试验制剂与参比制剂的生物等效性为98.0%(94.2%～101.9%)。结论:乌苯美司胶囊试验制剂与参比制剂生物等效。     

十一酸睾酮自微乳制剂的大鼠体内药代动力学研究

目的制备十一酸睾酮自微乳化制剂,并对其大鼠体内药代动力学进行研究。方法采用血清睾酮放免法测定给药后大鼠体内血清睾酮水平的变化,并计算药代动力学参数。结果十一酸睾酮原料药混悬液基本没吸收,而自微乳制剂和市售Andriol药物的吸收大大提高。以Andriol为参比制剂,自微乳制剂的相对生物利用度为96.4%。结论自微乳化给药系统能提高脂溶性药物十一酸睾酮的吸收。     

猕猴硬膜外及静脉注射 [~(125)I]虎纹毒素-1的药代动力学(英文)

目的　研究与比较猕猴硬膜外 (ed)及静脉 (iv)注射虎纹毒素 1后的药代动力学过程。方法　Iodogen法标记虎纹毒素 1 ,按 0 388MBq·kg- 1 的剂量向猕猴第 3和第 4腰椎之间硬膜外腔及静脉注射标记后虎纹毒素 1 ,用反相高效液相色谱检测猴血清中的药物放射性活度 ;γ 计数仪检测猴第 3和第 4腰椎硬膜外腔的药物放射性活度。结果　制备了具有生物活性的 [1 2 5I]虎纹毒素 1。硬膜外给药 1 0min后 ,给药部位局部硬膜外腔的药物放射性占总给药量的0 38,说明硬膜外给药是成功的 .硬膜外及静脉给药后 ,血药浓度分别在 30min和 2min达峰 ,分别为 (0 70± 0 0 4 )MBq·L- 1 和 (4 98± 0 58)MBq·L- 1 。两种给药途径的药时曲线不同 :猕猴硬膜外和静脉给药后 ,末端T12 分别为(1 0 36± 0 2 7)h和 (1 1 0 3± 1 1 6)h ;ClS 分别为 (1 2 9±0 0 7)L·h- 1 ·kg- 1 和 (1 2 5± 0 2 3)L·h- 1 ·kg- 1 ,硬膜外给予 [1 2 5I]HWTX 1的绝对生物利用度 (95± 5) %。结论　硬膜外和静脉两种给药方式下 ,[1 2 5I]虎纹毒素 1在猕猴体内的药代动力学过程具有差异性 ,两种给药方式下 [1 2 5I]在猕猴体内的分布与吸收特点对于虎纹毒素 I的临床药效学和毒理学研究提供了参考数据。     

AZTREONAM的药代动力学研究

6名健康志愿者分次接受肌注、静注和静滴Aztreonam 1g后,平均高峰血浓度分别为44.6、134.4和111.3μg/ml。三者的消除半衰期在1.8～1.9小时之间。肌注后吸收迅速完全,生物利用度约90％。24小时内尿排出率为给药量的70％。根据Aztreonam的药代动力学和抗菌活性,提出了治疗不同感染的给药方案。     

小干扰RNA(siRNA)药物药代动力学特征及生理药代动力学建模现状

小干扰RNA (small interfering RNA, siRNA)是以RNA干扰(RNAi)为基础的一类具有独特药代动力学特性和作用机制的药物,目前已有5种基于两种递送系统的siRNA药物上市获批,并且有越来越多的siRNA药物进入临床研究阶段。生理药代动力学(PBPK)建模是一种辅助药物开发和决策的可靠的工具,并且越来越被监管机构接受, PBPK模型在小分子和大分子领域广泛应用的背景下,在指导siRNA类药物开发方面仍然处于起步阶段。本文结合siRNA类药物的药代动力学特征,概述了siRNA类药物PBPK模型开发的现状及模型构建中所需的关键参数,以期为今后PBPK模型在siRNA类药物研发中的应用,及优化设计临床前试验获得关键数据提供一定的借鉴。     

国产氧氟沙星药代动力学研究

本文报道国产氧氟沙星药代动力学研究结果。用ＨＬＣ法测定血清药物浓度。８名健康志愿者口服４００ｍｇ氧氛沙星后，体内过程符合一室开放模型。血峰浓度于１．４７ｈ到达，为３．４８±０．７７μｇ／ｍｌ。ＡＵＣ为２５．３１±６．５０μｇ·ｈ／ｍｌ。半衰期为４．１３±０．８５ｈ。     

LC-MS方法研究氢溴酸高乌甲素在小鼠体内的药代动力学(英文)

本文建立了一种快速、灵敏的LC-MS法用于检测小鼠血浆中的高乌甲素浓度。采用ESI源和多反应监测(MRM)的方式进行检测,所选用的高乌甲素和内标延胡索乙素的反应离子对分别为m/z 585→535和m/z 356→m/z 192。该方法在3.0～2 000.0 ng·mL-1浓度内线性关系良好,定量下限为3.0 ng·mL-1,日内和日间精密度(RSD)均小于9.9%,准确度(RE)在±4.8%之内。氢溴酸高乌甲素分别以1.0、2.0和4.0 mg·kg-1单剂量静脉注射给予小鼠后,t1/2分别为0.47、0.48和0.49 h,AUC0-t分别为55.5、110.5和402.9 ng·h·mL-1。实验结果表明,氢溴酸高乌甲素单剂量静脉注射给予小鼠后,在低剂量(1.0～2.0 mg·kg-1)范围内其药动学行为符合线性动力学特征,当给药剂量(2.0 mg·kg-1)增大至4.0 mg·kg-1时,AUC增加至约4倍,而Vz和CL却显著降低,呈现非线性动力学特征,可能与高浓度下药物血浆蛋白结合率的降低有关。     

新生儿抗生素药代动力学研究

抗生素在新生儿中代谢无论从哪个角度考虑均不同于儿童和成年人。早产儿和足月儿也有较大的区别。某些原因影响新生儿抗生素的药代动力学,例如循环、呼吸、肾和肝功能改变与出生和过期月龄有关,而其他一些因素,例如在疾病或感染时发生脱水、酸中毒、发热、缺氧和呼吸衰竭。从生理学来说,新生儿肌肉和脂肪组织储存少,比婴儿的皮肤薄和渗透性好,并且有一个相对大的表面积。新生儿脑、心、肝和肾也相对较大,使体内水的容量增加。这些差异在患病早产儿中尤其显著,可能在抗生素的代谢方式上有重要影响。     

The effect of the fat content of food on the pharmacokinetics and pharmacodynamics of SDZ FOX 988, an antidiabetic agent,in the dog

SDZ FOX 988 (FOX 988) is being developed for the treatment of type II diabetes. The objective of this study was to examine the effect of the fat content of food on the pharmacokinetics and pharmacodynamics of FOX 988 following oral administration in the dog. In a randomized, cross-over design, four dogs received a single 10 mg kg^?1 dose of ¹⁴C-FOX 988 suspension concomitantly with food containing 10% fat or 40% fat, or with the 10% fat food at 4 h post-dose. Serial blood, urine, and fecal samples were collected for 96 h and analyzed for total radioactivity. Blod concentrations of 53–450, the active metabolite of FOX 988, were also determined. Serum concentrations of β-hydroxybutyrate and glucose, pharmacological markers for the antidiabetic effects, were measured serially for 24 h after dosing. The animals receiving the low-fat meal at dosing and at 4 h post-dose exhibited similar extents of absorption, as shown by similar AUC values and urianry radioactivity recovery. Administration of the high-fat meal at dosing significantly enhanced the absorption of FOX 988 and resulted in high blood concentrations of 53–450. However, no significant differences in the pharmacological activity of the drug were observed among the three treatments.     

奈韦拉平纳米混悬液的制备及大鼠体内药动学研究

目的：：制备奈韦拉平纳米混悬剂,考察其在大鼠口服给药后体内的药动学特征。方法：采用高压均质法制备奈韦拉平纳米混悬剂,以纳米混悬剂粒径分布、PdI和Zeta电位为指标,考察了奈韦拉平纳米混悬剂的影响因素,并对制得的纳米粒进行表征;采用高效液相色谱法测定大鼠血浆中的奈韦拉平浓度,使用3P97软件计算相应的药动学参数。结果：奈韦拉平纳米混悬液平均粒径为(456.1±72.1) nm,PdI为(0.441±0.072),Zeta电位为(-24.4±4.7) mV。奈韦拉平混悬液和奈韦拉平纳米混悬剂在大鼠体内的AUC0-12分别为(7.57±0.52)和(11.72±1.83) mg·h·L-1;t1/2分别为(2.45±0.31)和(3.16±0.39) h;Tmax分别为(1.43±0.38)和(1.61±0.32) h;Cmax分别为(1.62±0.42)和(3.15±0.52) mg·L-1。结论：奈韦拉平纳米混悬液能够明显改善大鼠体内奈韦拉平的药动学行为,与奈韦拉平混悬液相比显著提高了药物的生物利用度。     

异钩藤碱药动学及其含量测定方法研究概述△

目的:归纳异钩藤碱药动学及其含量测定方法的研究进展。方法:查阅国内外有关文献进行综合分析。结果:异钩藤碱是中药钩藤中的主要生物碱之一,目前主要采用HPLC、反相HPLC等方法检测动物组织和血液中异钩藤碱浓度,并进行了异钩藤碱在大鼠、兔、猫体内的药动学研究;采用HPLC、超高效液相色谱、非水毛细管电泳、高效毛细管电泳、薄层色谱傅里叶变换表面增强拉曼散射法测定钩藤药材中异钩藤碱的含量。结论:虽然对异钩藤碱药动学及其含量检测方法研究取得了一定成果,随着科技发展和高端检测仪器的应用,还需采用更加快速、便捷、精确的检测方法,为异钩藤碱今后的进一步研究和开发提供技术支撑。     

天然维生素E纳米乳的制备及其性质考察

目的:制备天然维生素E纳米乳并对其性质进行考察。方法:通过单因素考察和正交试验设计优选天然维生素E纳米乳的制备工艺和最佳处方,并通过形态、粒径、Zeta电位、pH值的测定研究其性质。结果:天然维生素E纳米乳的最佳处方为注射用油5 g,蛋黄卵磷脂1.5 g,F68 4 g,油酸0.25 g。所制备的乳剂外观呈乳白略带黄色,有蓝色乳光,平均粒径为87.7 nm,PI为0.287,Zeta电位为-23.5 mV,pH值为6.79。结论:本实验制备的天然维生素E纳米乳符合注射用制剂的要求。     

Modelling the pharmacokinetics and pharmacodynamics of trimazosin

The pharmacokinetics and pharmacodynamics of trimazosin are described following both intravenous and oral administration to 6 normotensive, male volunteers. The IV and oral drug and metabolite (1-hydroxytrimazosin) concentration data are fitted simultaneously to the same pharmacokinetic model. The pharmacodynamic response, change in systolic blood pressure following 5 min in the erect posture, is described using several possible models. The most efficient is one which attributes the response to both the parent drug and its principal metabolite. The response following oral administration is also consistent with this model. It appears that the reduction in blood pressure following administration of trimazosin at steady state may be governed by the concentration of metabolite.     

Preparation,characterization and pharmacokinetics of 10-hydroxy-camptothecin nanosuspension

10-Hydroxycamptothecin (HCPT) is a broad-spectrum anticancer drug, while its low solubility and instability severely limit its application. In this study, HCPT nanosuspension (HCPT-NSP), also known as nanocrystal, was prepared by micro-precipitationcombined with high-pressure homogenization method. This nanosuspension was characterized by size, shape, zeta potential, drug loading efficiency and in vitro drug release behavior. Preferred formulation and process showed that particle size was (129.8±13.9) nm, PDI was 0.20±0.07, and drug loading efficiency was 36.5%±9.5%. Moreover, HCPT nanocrystal concentration reached(1.35±0.2) mg/mL in HCPT-NSP, which was more than 1000-fold higher than that of HCPT. Transmission electron microscopy (TEM) results showed that the nanosuspension was short rod in shape. X-ray powder diffraction (XRD), thermogravimetric analysis (TGA), derivative thermogravimetric analysis (DTA) and differential scanning calorimetry (DSC) further elaborated the crystal state of the HCPT. The drug concentration-time curve of HCPT-NSP in rats was in accordance with the three-compartment model, showing prolonged half-life. Taken together, our data suggested that HCPT-NSP was a promising drug delivery system.     

Pilot study in humans on the pharmacokinetics and safety of propofol 6% SAZN

In a pilot study on the first application of Propofol 6% SAZN in humans, the pharmacokinetics and safety of the new product seem to be similar to those of Propofol 1% SAZN and Diprivan®10 after bolus injection. The results will have to be confirmed in a larger clinical study in order to develop Propofol 6% SAZN as an alternative for Diprivan®10.     

白藜芦醇微乳的制备及表征

目的:采用高压均质法制备白藜芦醇微乳,并对其进行表征。方法:以白藜芦醇微乳粒径分布、多分散系数(Pd I)、包封率为评价指标,考察制备白藜芦醇微乳的各个因素,并对制得的微乳进行表征;初步研究白藜芦醇微乳的稳定性。结果:白藜芦醇微乳的平均粒径为231±37.8 nm,Pd I为0.228±0.047,zeta电位为-42.5±4.3 m V;透射电镜显示微乳粒径均一,成球状分布。长期稳定性研究显示,微乳在25℃条件下放置3个月稳定。结论:高压均质法制备白藜芦醇微乳工艺简单易行。