盐酸曲马多缓释片的制备及其在健康人体内的药动学研究

制备了曲马多缓释片（100mg／片）,以缓释度为指标筛选出了曲马多缓释片的处方,并对该处方缓释片与市售同品种对照进行了人体单剂量及多剂量随机交叉给药药动学研究。用高效液相荧光色谱法测定了血浆中的药物浓度。单剂量口服自制缓释片的药动力学参数Tmax、Cmax、AUC0→∞分别为4．6±1．4h、287．83±53．83ng／mL、4487．92ng／mL·h。多剂量口服自制缓释片的药动力学参数（Tmax、Cssmax、AUC0→τT分别为3．0±0．7h、397．46±117．05ng／mL、5161．14±1774．92ng／mL·h。并且考察了该制剂的体外释放度,结果表明,该药体外释放速度平稳。     

溃疡汤对大鼠体内奥美拉唑药动学的影响

目的考察溃疡汤干预后,大鼠肝微粒体CYP2C19活性的变化。方法大鼠经溃疡汤预处理后,分别于体内和体外考察奥美拉唑在预处理大鼠体内药动学。结果大鼠经溃疡汤干预后,奥美拉唑的药动学参数显示MRT和t_(1/2z)显著降低,CL_z显著升高,差异具有极显著统计学意义(P0.01),溃疡汤组大鼠的AUC也成降低趋势。预处理大鼠肝微粒CYP2C19的表达提高。结论初步推断溃疡汤可能诱导CYP 2C19酶的活性。     

槲皮素嵌段共聚物胶束大鼠体内药动学研究

目的研究槲皮素嵌段共聚物胶束在大鼠体内的药动学。方法采用薄膜分散法制备槲皮素嵌段共聚物胶束。以槲皮素溶液剂为对照,考察胶束大鼠静脉注射后的药动学。采用3p97程序计算药动学参数。结果胶束在大鼠体内过程符合二室模型,其中溶液剂的t1/2β为9.15±4.91 min,AUC为36.55μg·min·m L-1;胶束t1/2β为40.28±2.53 min;AUC为84.97μg·min·m L-1。结论胶束能明显延长槲皮素在体内滞留时间,提高药物的生物利用度。     

液相色谱-化学发光联用技术在中药酚类活性成分药动学中的应用研究

液相色谱-化学发光联用技术(HPLC-CL)是利用液相色谱高效分离和化学发光反应高灵敏检测结合的联用技术,具有较高的灵敏度、选择性等优点,在医药分析领域应用广泛。我国中药成分很多以酚类为主,其中酚类活性成分生物学活性广泛,成为研究的热点。中药酚类活性成分药物含量较低、干扰组分多,在药动学分析上要求较高。文章采用液相色谱-化学发光联用技术的优势分析中药酚类活性成分山奈酚,并进行药动学研究。     

α-细辛脑前体脂质体的制备及其在大鼠体内药动学研究

目的:制备α-细辛脑前体脂质体,研究其在大鼠体内药动学行为。方法:采用载体沉积法制备α-细辛脑前体脂质体;经超声雾化给药后,PKSolver软件计算药动学参数。结果:脂质体包封率为95.88%±1.3%;药动学参数为t1/2α=26.93±6.38 min,Tmax=12.03±3.26 min,Cmax=1.81±0.20 mg/L,AUC0-t=132.40±19.26 mg·min/L,绝对生物利用度为50.52%。结论:制备包封率高的α-细辛脑前体脂质体,并显著延长α-细辛脑在大鼠体内消除半衰期和提高绝对生物利用度。     

DNJ双层渗透泵片的制备及比格犬体内药动学研究

制备了1-脱氧野尻霉素（DNJ）双层渗透泵片,以释放度为评价指标优化了处方,考察了DNJ双层渗透泵片的体外释药性,并对比研究了DNJ双层渗透泵片和速释片在比格犬体内的药动学。DNJ双层渗透泵片的最优处方为含药层羟丙基甲基纤维素（HPMC） E50用量为10 mg、助推层聚氧乙烯（PEO,M_r 6×10⁶）用量为80 mg 、包衣层醋酸纤维素（CA）用量为15 mg及聚乙二醇（PEG）4000用量为5 mg,在此条件下DNJ溶出速度最为适宜,并且不受pH值的变化影响,药物12 h溶出完全,且恒速缓慢释放。对比DNJ双层渗透泵片和速释片在比格犬体内的双制剂双周期交叉试验,结果表明：双层渗透泵片释放的达峰时间（t_max）为（9.3±3.8）h比速释片（4.4±2.2）h显著延迟,达到了缓控释的目的,渗透泵片的相对生物利用度为（96.1±9.8）%,90%置信区间为84.8%~103.7%,渗透泵片与速释片吸收程度生物等效。     

薄膜-超声法制备黄芩苷脂质体及其大鼠体内药动学研究

目的:制备黄芩苷脂质体,进行体外质量评价及其在大鼠体内的药动学研究。方法:采用薄膜分散法制备黄芩苷脂质体,以包封率作为评价指标,通过BBD设计-效应面法,得到最佳制备的工艺参数和处方,并测定脂质体的粒径分布、包封率以及在体外药物释放情况;通过大鼠尾静脉注射黄芩苷溶液及黄芩苷脂质体溶液,分析大鼠体内的药动学参数变化情况。结果:黄芩苷脂质体的最佳工艺处方:大豆卵磷脂药物质量比例4.9∶1,大豆卵磷脂胆固醇质量比例7.53∶1,水化体积为8.07 m L;黄芩苷脂质体平均粒径在176 nm,平均包封率为41.31%,黄芩苷脂质体具有一定的缓释作用;黄芩脂质体组在大鼠体内的半衰期(t_1/2)延长,药时曲线下面积AUC(0～t)、AUC(0～∞)增加以及体内平均滞留时间延长,说明将黄芩苷制备成脂质体后作用可提高药物的疗效。结论:制备的黄芩苷脂质体具备一定的缓释性能,对黄芩苷新剂型的开发及临床研究具有重要意义。     

HPLC-MS/MS法测定美金刚体内浓度及药代动力学研究

建立高效液相色谱-串联质谱(HPLC-MS/MS)方法测定大鼠血浆中美金刚,并用于美金刚双羟萘酸混悬剂的体内药动学研究。大鼠肌肉注射美金刚双羟萘酸混悬剂,在预设的时间点采集血浆样本,经沉淀蛋白后进行UPLC-MS/MS分析。用0.1%甲酸水溶液和甲醇梯度洗脱,Shim-pack GIST C18色谱柱分离,电喷雾离子源,正离子方式检测,选择多反应监测模式。结果显示该方法符合方法学要求,自制美金刚双羟萘酸盐混悬剂的药动学也为美金刚长效注射剂的设计提供了参考。     

美洛昔康血浆样品分析方法验证及药动学研究

建立美洛昔康在大鼠体内样品的分析方法并验证，以用于美洛昔康制剂的体内药代动力学研究。以吡咯昔康为内标，液液-萃取法处理体内血浆样品，通过高效液相色谱法(HPLC)进行含量测定。结果显示，该方法专属性好，最低定量下线可达0.5μg/mL,线性范围为0.5～100μg/mL,精密度、准确度及提取回收率均符合质量标准，可用于美洛昔康制剂的药动学研究，为临床镇痛制剂的开发提供参考。     

氨茶碱在大鼠体内的药代动力学研究

用高效液相色谱法研究氨茶碱在大鼠体内的药代动力学.色谱柱为Hypersil BDS C18 (4.6 mm×200mm,5 μm),流动相为甲醇—水(24 ∶ 76),检测波长为274 nm.结果表明,大鼠灌胃给予氨茶碱后,其代谢符合二室模型;由统计矩参数表示的主要药代动力学参数如下:tmax=(1.083士0.195...     

Microanalysis,Pharmacokinetics and Tissue Distribution of Polysaccharide-Protein Complexes from Longan Pulp in Mice

A high performance size exclusion-fluorescence detection (HPSEC-FD) method combined with fluorescein isothiocyanate (FITC) prelabeling was established for the microanalysis of polysaccharide–protein complexes from longan pulp (LPP). FITC-labeled LPP (LPPF) was fractionated by gel filtration chromatography. The weight-average molecular weight and FITC substitution degree of LPPF were 39.01 kDa and 0.20%, respectively. The HPSEC-FD calibration curves linear over the range of 1–200 µg/mL in mouse plasma, spleen and lung samples with correlation coefficients greater than 0.995. The inter-day and intra-day precisions of the method were not more than 6.9%, and the relative recovery ranged from 93.7% to 106.4%. The concentration–time curve of LPPF in plasma following intravenous (i.v.) administration at 40 mg/kg body weight well fitted to a two-compartment model. LPPF rapidly eliminated from plasma according to the short half-lives (t_1/2α = 2.23 min, t_1/2β = 39.11 min) and mean retention times (MRT_0–t = 1.15 h, MRT_0–∞ = 1.39 h). After administration over 5 to 360 min, the concentration of LPPF in spleen homogenate decreased from 7.41 to 3.68 µg/mL; the concentration in lung homogenate decreased from 9.08 to 3.40 µg/mL. On the other hand, the increasing concentration of LPPF fraction with low molecular weight in heart homogenate was observed.     

Pharmacokinetics and tissue distribution study of praeruptorin d from radix peucedani in rats by high-performance liquid chromatography (HPLC)

Praeruptorin D (PD), a major pyranocoumarin isolated from Radix Peucedani, exhibited antitumor and anti-inflammatory activities. The aim of this study was to investigate the pharmacokinetics and tissue distribution of PD in rats following intravenous (i.v.) administration. The levels of PD in plasma and tissues were measured by a simple and sensitive reversed-phase high-performance liquid chromatography (HPLC) method. The biosamples were treated by liquid-liquid extraction (LLE) with methyl tert-butyl ether (MTBE) and osthole was used as the internal standard (IS). The chromatographic separation was accomplished on a reversed-phase C(18) column using methanol-water (75:25, v/v) as mobile phase at a flow rate of 0.8 mL/min and ultraviolet detection wave length was set at 323 nm. The results demonstrate that this method has excellent specificity, linearity, precision, accuracy and recovery. The pharmacokinetic study found that PD fitted well into a two-compartment model with a fast distribution phase and a relative slow elimination phase. Tissue distribution showed that the highest concentration was observed in the lung, followed by heart, liver and kidney. Furthermore, PD can also be detected in the brain, which indicated that PD could cross the blood-brain barrier after i.v. administration.     

Identification and Pharmacokinetics of Multiple Potential Bioactive Constituents after Oral Administration of Radix Astragali on Cyclophosphamide-Induced Immunosuppression in Balb/c Mice

Radix Astragali (RA) is one of the commonly-used traditional Chinese medicines (TCMs) with an immunomodulatory effect confirmed in the clinic. In order to better understand the material basis for the therapeutic effects, this study was to investigate the absorbed components and their pharmacokinetic profile after oral administration of RA on cyclophosphamide-induced immunosuppression in Balb/c mice. As a result, 51 compounds in RA extract and 31 prototype compounds with nine metabolites were detected in mice plasma by the ultra-fast liquid chromatography (UFLC)-DAD-Q-TOF-MS/MS method. The pharmacokinetic parameters of five main constituents, including calycosin-7-O-glucoside, ononin, calycosin, formononetin and astragaloside IV, were obtained using HPLC-MS/MS. These results offered useful information for research on the pharmacological mechanism of RA and for its further development.     

手性药物的药代动力学

手性药物对映体在体内的手性环境中表现出强烈的立体选择性,对映体之间表现出不同的药动学和药效学性质。研究手性药物对映体的药动学差异,讨论吸收、分布、代谢、排泄4个环节中的药动学差异,对影响这些差异的因素逐一分析。     

蒽醌在正常及酒精肝损伤大鼠的药动学比较

比较栀子大黄汤中芦荟大黄素,大黄酸,大黄酚及大黄素甲醚在正常、酒精肝损伤大鼠药代动力学过程。给予大鼠灌服50%乙醇,连续十天,建立酒精肝损伤模型。采用HPLC-FLD法测定大鼠灌服栀子大黄汤不同时间点蒽醌血药浓度。模型组中芦荟大黄素、大黄酸、大黄酚、大黄素甲醚Cmax,AUC0~t显著低于正常组(P0.05)。酒精所致肝损伤能够阻碍栀子大黄汤中蒽醌成分的吸收,降低血浆暴露率。     

Methylone and MDMA Pharmacokinetics Following Controlled Administration in Humans

The aim of this study is to define, for the first time, human methylone and HMMC plasma pharmacokinetics following controlled administration of 50–200 mg methylone to 12 male volunteers. A new LC-MS/MS method was validated to quantify methylone, MDMA, and their metabolites in plasma. The study was a randomized, cross-over, double-blinded and placebo-controlled study, with a total of 468 plasma samples collected. First, 10 µL of MDMA-d₅, MDA-d₅ and methylone-d₃ internal standards were added to 100 µL of plasma. Two mL of chloroform and ethyl acetate 9:1 (v/v) were then added, mixed well and centrifuged. The supernatant was fortified with 0.1 mL acidified methanol and evaporated under nitrogen. Samples were reconstituted with a mobile phase and injected into the LC-MS/MS instrument. The method was fully validated according to OSAC guidelines (USA). Methylone plasma concentrations increased in a dose-proportional manner, as demonstrated by the increasing maximum concentration (Cmax) and area under the curve of concentrations (AUC). Methylone Cmax values were reported as 153, 304, 355 and 604 ng/mL, AUC0–24 values were reported as 1042.8, 2441.2, 3524.4 and 5067.9 h·ng/mL and T_1/2 values as 5.8, 6.4, 6.9 and 6.4 h following the 50, 100, 150 and 200 mg doses, respectively. Methylone exhibited rapid kinetics with a Tmax of 1.5 h for the 50 mg dose and 2 h approximately after all the other doses. HMMC exhibited faster kinetics compared to methylone, with a Cmax value that was 10–14-fold lower and an AUC0–24 value that was 21–29-fold lower. Methylone pharmacokinetics was linear across 50–200 mg oral doses in humans, unlike the previously described non-linear oral MDMA pharmacokinetics. An LC-MS/MS method for the quantification of methylone, MDMA and their metabolites in human plasma was achieved. Methylone exhibited linear pharmacokinetics in humans with oral doses of 50–200 mg.     

葡萄球菌S-35对小鼠的毒性作用

[目的]对葡萄球菌S-35进行动物安全性评价。[方法]采用Ames体外试验、小鼠急性毒性试验、小鼠精子畸形试验、小鼠骨髓嗜多染红细胞微核试验及小鼠30 d喂养慢性毒性检测等方法,测定了该菌株对小鼠的毒性、血液生化指标、血项指标及脏器的影响,并做组织切片观察。[结果]在1.6×10^10~2×10^12 cfu/皿剂量范围内,葡萄球菌S-35 Ames体外试验结果为阴性;葡萄球菌S-35对小鼠的急性经口毒性为“低毒”级(LD50>4640 mg/kg);S-35在0.78~12.5 mg/L试验剂量范围内,小鼠精子畸形和骨髓细胞微核试验结果为阴性。小鼠30 d喂养试验,葡萄球菌S-35在125 mg/L的剂量下,小鼠血液生化和血项各项指标均无异常。[结论]葡萄球菌S-35对动物机体安全,该菌株有进一步研究开发为生防菌的价值。