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991.
目的考察注射用奥沙利铂纳米结构脂质载体(OP NLC)冻干粉末处方及工艺。方法通过单因素实验优选冻干制剂的处方工艺,并评价其制剂学性质。结果以5%甘露醇溶液作为冻干保护剂,确定最终的冻干工艺。冻干后制剂粒径(124±16) nm,Zeta电位-10.8 mV,包封率67.3%,与冻干前[粒径(115±17) nm,Zeta电位-16.0 mV,包封率72.6%]相比,无明显变化。结论在优选的冻干工艺条件下可制得稳定的奥沙利铂纳米结构脂质载体冻干制剂。 相似文献
992.
Dong-mei Zhang Kun Wang Xia Zhao Yun-fei Li Qing-shan Zheng Zi-ning Wang Yi-min Cui 《Acta pharmacologica Sinica》2012,33(11):1387-1394
Aim:
To investigate the population pharmacokinetics (PK) and pharmacodynamics (PD) of bivalirudin, a synthetic bivalent direct thrombin inhibitor, in young healthy Chinese subjects.Methods:
Thirty-six young healthy volunteers were randomly assigned into 4 groups received bivalirudin 0.5 mg/kg, 0.75 mg/kg, and 1.05 mg/kg intravenous bolus, 0.75 mg/kg intravenous bolus followed by 1.75 mg/kg intravenous infusion per hour for 4 h. Blood samples were collected to measure bivalirudin plasma concentration and activated clotting time (ACT). Population PK-PD analysis was performed using the nonlinear mixed-effects model software NONMEM. The final models were validated with bootstrap and prediction-corrected visual predictive check (pcVPC) approaches.Results:
The final PK model was a two-compartment model without covariates. The typical PK population values of clearance (CL), apparent distribution volume of the central-compartment (V1), inter-compartmental clearance (Q) and apparent distribution volume of the peripheral compartment (V2) were 0.323 L·h-1·kg-1, 0.086 L/kg, 0.0957 L·h-1·kg-1, and 0.0554 L/kg, respectively. The inter-individual variabilities of these parameters were 14.8%, 24.2%, fixed to 0% and 15.6%, respectively. The final PK-PD model was a sigmoid Emax model without the Hill coefficient. In this model, a covariate, red blood cell count (RBC*), had a significant effect on the EC50 value. The typical PD population values of maximum effect (Emax), EC50, baseline ACT value (E0) and the coefficient of RBC* on EC50 were 318 s, 2.44 mg/L, 134 s and 1.70, respectively. The inter-individual variabilities of Emax, EC50, and E0 were 6.80%, 46.4%, and 4.10%, respectively.Conclusion:
Population PK-PD models of bivalirudin in healthy young Chinese subjects have been developed, which may provide a reference for future use of bivalirudin in China. 相似文献993.
Guo-fu Li Kun Wang Rui Chen Hao-ru Zhao Jin Yang Qing-shan Zheng 《Acta pharmacologica Sinica》2012,33(11):1359-1371
Aim:
To develop and evaluate a whole-body physiologically based pharmacokinetic (WB-PBPK) model of bisoprolol and to simulate its exposure and disposition in healthy adults and patients with renal function impairment.Methods:
Bisoprolol dispositions in 14 tissue compartments were described by perfusion-limited compartments. Based the tissue composition equations and drug-specific properties such as log P, permeability, and plasma protein binding published in literatures, the absorption and whole-body distribution of bisoprolol was predicted using the ''Advanced Compartmental Absorption Transit'' (ACAT) model and the whole-body disposition model, respectively. Renal and hepatic clearances were simulated using empirical scaling methods followed by incorporation into the WB-PBPK model. Model refinements were conducted after a comparison of the simulated concentration-time profiles and pharmacokinetic parameters with the observed data in healthy adults following intravenous and oral administration. Finally, the WB-PBPK model coupled with a Monte Carlo simulation was employed to predict the mean and variability of bisoprolol pharmacokinetics in virtual healthy subjects and patients.Results:
The simulated and observed data after both intravenous and oral dosing showed good agreement for all of the dose levels in the reported normal adult population groups. The predicted pharmacokinetic parameters (AUC, Cmax, and Tmax) were reasonably consistent (<1.3-fold error) with the observed values after single oral administration of doses ranging from of 5 to 20 mg using the refined WB-PBPK model. The simulated plasma profiles after multiple oral administration of bisoprolol in healthy adults and patient with renal impairment matched well with the observed profiles.Conclusion:
The WB-PBPK model successfully predicts the intravenous and oral pharmacokinetics of bisoprolol across multiple dose levels in diverse normal adult human populations and patients with renal insufficiency. 相似文献994.
Yun-fei Li Kun Wang Fang Yin Ying-chun He Ji-han Huang Qing-shan Zheng 《Acta pharmacologica Sinica》2012,33(11):1424-1430
Aim:
To find an appropriate dose regimen of the novel antibacterial agent antofloxacin for a phase II clinical trial using a population pharmacokinetic (PPK) study in healthy volunteers and the minimum inhibitory concentration (MIC) as pharmacodynamic (PD) parameters.Methods:
Twenty-four healthy volunteers were enrolled in a double-blind crossover study and received antofloxacin (200 or 400 mg/d, po) for consecutive 5 d with 10 d washout between two separate periods. Blood concentrations were analyzed using HPLC with a UV-Vis detector. The values of area under the curve (AUC) with covariates were obtained from a PPK model, and the MICs came from the previous in vitro studies. The dose regimen was determined for the phase II clinical trial according to the ratio (>20) of AUC/MIC, and the efficacy of the dose was evaluated by the trial.Results:
A two-compartment model best described the time-concentration data with first-order absorption. The PPK parameter estimates for CL, Vc, Q, Vp and KA are 8.34 L/h, 142 L, 15.9 L/h, 52.2 L and 4.64 1/h, respectively. The covariates sex for KA, weight for CL, weight for Vc and interoccasion variability were included in the final model. The AUC/MIC was calculated based on the PPK model and the MIC of antofloxacin for Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus and Staphylococcus epidermidis were determined in previous researches. The 400 mg loading dose with 200 mg/d maintenance dose was recommended and confirmed by the phase II trial.Conclusion:
The ratio of AUC from the PPK model vs MIC as the PD parameter can be applied in a dose-finding trial of antofloxacin in treatment of bacterial infections. The PPK model suggests that sex and body weight may be considerations in regards to individual therapy, which should be investigated in larger clinical trials and serve as a potential reference for clinical therapies. 相似文献995.
目的改良前、中路的颈内静脉穿刺置管方法并进行临床验证对比。方法选择我院适合颈内静脉穿刺置管患者共456例,采用国际肥胖指数标准选择穿刺点后分成改良前、中路法与传统前、中路法进行穿刺置管对比研究。结果改良前、中路法的穿刺置管成功率为100%,改良组与传统组比较,在一针穿刺成功率、误穿动脉率,经χ2检验,P<0.01,血气胸发生率P<0.05,存在显着差异。结论改良前、中路的颈内静脉穿刺置管方法,具有针对个体差异定位准确,操作简单快捷,穿刺成功率高,并发症少等优点,是值得推广的颈内静脉穿刺置管方法。 相似文献
996.
JIANG Li-ying TANG Su-su WANG Xiao-yun LIU Li-ping LONG Yan HU Mei LIAO Ming-xing DING Qi-long HU Wei LI Jia-chang HONG Hao . 《中国药理学与毒理学杂志》2012,(3):437
OBJECTIVE Pioglitazone,known as a peroxisome proliferator-activated receptor γ(PPARγ) agonist,is used to treat type 2 diabetes(T2DM).T2DM has been associated with reduced performance on numerous domains of cognitive function.Here,we investigated the effects of pioglitazone on memory impairment in a mouse model with defects in insulin sensitivity and secretion,namely high-fat diet(HFD) streptozotocin(STZ)-induced diabetic mice.METHODS ICR mice were fed an HFD for 4 weeks and then injected with a single low dose of STZ followed by continued HFD feeding for an additional 4 weeks.The diabetic mice were orally administered with pioglitazone(9,18 mg·kg-1) for 4-5 weeks.Y-maze test and Morris water maze test(MWM) were employed for testing learning and memory.Serum glucose,serum insulin,serum triglyceride,brain amyloid peptide-β(Aβ),brain β-site amyloid precursor protein cleaving enzyme(BACE1),brain nuclear factor κB(NF-κB),brain receptor for advanced glycation end products(RAGE) were also tested.RESULTS The STZ/HFD diabetic mice,characterized by hyperglycemia,hyperlipemia and hypoinsulinemia,performed poorly on Y-maze and MWM hence reflecting impairment of learning and memory behavior with increases of Aβ40/Aβ42,BACE1,NF-κB,and RAGE in brain.Treatment of PPARγ agonist,pioglitazone,significantly reversed diabetes-induced impairment of learning and memory behavior,which is involved in decreases of Aβ40/Aβ42 via inhibition of NF-κB,BACE1 and RAGE in brain as well as attenuation of hyperglycemia,hyperlipemia and hypoinsulinemia.CONCLUSION It is concluded that PPARγ agonist pioglitazone may be considered as potential pharmacological agents for the management of cognitive dysfunction in T2DM. 相似文献
997.
目的:建立同时测定复方儿茶酊中儿茶素与原儿茶素含量的方法。方法:采用高效液相色谱法。色谱柱为YMC ODS(250mm×4.6mm,5μm),流动相为0.04mol·L-1枸橼酸溶液-N,N-二甲基甲酰胺-四氢呋喃(45∶8∶2,V/V/V),流速为1.0mL·min-1,检测波长为280nm,柱温为35℃。结果:儿茶素与原儿茶素的检测浓度分别在0.0518~0.2590、0.0101~0.2030mg·mL-1(r均为0.9999)范围内与各自峰面积积分值呈良好的线性关系;平均加样回收率分别为101.63%和100.49%,RSD分别为1.27%和1.12%(n均为9)。结论:本方法简便、准确、稳定,能有效控制复方儿茶酊的质量。 相似文献
998.
目的:探讨头孢克肟致药品不良反应(ADR)发生的特点及规律。方法:收集国内医药期刊有关头孢克肟致ADR个案报道10例并汇总3家医院2000-2010年上报的头孢克肟致ADR报告79例,共89例,进行分析、评价。结果:ADR临床表现方面,以皮肤及其附件损害居首位(占41.57%),其次为神经系统损害(占19.10%)及消化系统损害(占15.73%);以≤10岁儿童(48.31%)和序贯用药(46.07%)报道率最高;约38.20%的ADR发生在用药48h后。结论:临床应重视头孢克肟引起的ADR,用药时应加强对患者的观察,以减少严重ADR的发生。 相似文献
999.
分子印迹技术是一门分子识别技术,由于其制备的分子印迹聚合物对目标分子具有特异性识别的功能,在中药领域受到了广泛关注。本文综述了分子印迹技术的原理、特点、聚合物的制备方法及其在中药现代化研究中的应用。 相似文献
1000.
目的:观察阿米卡星对肾小管上皮细胞的损伤及热休克蛋白70表达的影响。方法:常规培养人肾小管上皮细胞系HK-2细胞,给予阿米卡星(100μg·mL-1)损伤或MnCl2(2μg·mL-1)保护,于24,48,72,96 h时分光光度法测定细胞增殖,乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)、丙二醛(MDA)、N-乙酰-β氨基葡萄糖苷酶(NAG)含量,逆转录多聚酶链式反应(RT-PCR)法检测HSP70 mRNA表达,Western-blot检测HSP70蛋白表达。结果:阿米卡星损伤HK-2细胞后,细胞增殖显著减少,LDH释放量、NAG含量、MDA含量增加显著,SOD活力明显下降,HSP70 mRNA及其蛋白的表达显著增加(与对照组比,P<0.01);给予MnCl2干预后,HK-2细胞的细胞增殖明显有所恢复,LDH释放量、NAG含量、MDA含量有所下降,SOD活力有所增加,HSP70 mRNA及其蛋白的表达有所下降(与损伤组比,P<0.01)。结论:阿米卡星的肾脏毒性与HSP70的表达存在密切的联系。 相似文献