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31.
目的利用固体分散技术改善环孢素A(CsA)的溶解性能,提高其体外溶出速率。方法以Poloxamer188为载体,溶剂熔融法制备不同比例组成的环孢素A固体分散体,考察体外溶出速率及不同转速和不同溶出介质对溶出的影响,并配合X-射线粉末衍射分析药物在载体中的存在状态。对溶出度结果用Weibull分布模型进行拟合,计算体外溶出主要参数td和t50,并进行方差分析。结果CsA在药物-载体比例为1:4或1:6的固体分散体中呈非晶态。固体分散体的溶出速率与相应物理混合物及原料药间存在极显著差异(P<0.01),溶出介质对药物溶出无显著性影响(P>0.05)。结论制成固体分散体能显著提高CsA的溶出速率。 相似文献
32.
目的以环孢素A为模型药物,研究微乳制剂在药剂学上的应用.方法根据微乳的拟三元相图,筛选微乳的处方,制备环孢素A微乳,以冷冻蚀刻电镜法和动态光散射法分别考察其形态和粒径,采用高效液相方法测定微乳中环孢素A浓度,考察含量及稳定性.结果环孢素A微乳制备简单,粒径分布均匀,是一稳定的制剂.结论微乳在药学上有广阔的应用前景. 相似文献
33.
Activation of central GABAB receptors offsets the cyclosporine counteraction of endotoxic cardiovascular outcomes in conscious rats 下载免费PDF全文
Marwa Y. Sallam Sahar M. El‐Gowilly Abdel‐Galil A. Abdel‐Galil Mahmoud M. El‐Mas 《Fundamental & clinical pharmacology》2018,32(5):485-498
We have previously shown that cyclosporine (CSA) counteracts cardiovascular manifestations induced by endotoxemia (lipopolysaccharide, LPS) such as hypotension and cardiac autonomic dysfunction in conscious rats. In this study, we investigated whether the facilitation of central γ‐amino butyric acid (GABA) neurotransmission blunts these favorable influences of CSA. The LPS‐CSA interaction was determined in the absence and presence of drugs that activate GABAA or GABAB receptors or elevate synaptic GABA levels in the central nervous system. The consequent i.v. administration of CSA (10 mg/kg) blunted the LPS‐evoked hypotension, tachycardia, and reductions in time‐ and frequency‐domain indices of heart rate variability (measures of cardiac autonomic control) evoked by LPS (10 mg/kg i.v.). The ability of CSA to reverse the LPS effects disappeared in rats treated intracisternally (i.c.) with baclofen (selective GABAB agonist, 2 μg/rat) but not muscimol (selective GABAA agonist, 1 μg/rat), indicating a preferential compromising action for central GABAB receptors on the advantageous effects of CSA. Moreover, the improvement by CSA of LPS‐evoked cardiovascular derangements was also eliminated after concurrent i.c. administration of vigabatrin (GABA transaminase inhibitor, 200 μg/rat) or tiagabine (GABA reuptake inhibitor, 100 μg/rat). These results demonstrate that the activation of central GABAB receptors either directly via baclofen or indirectly following interventions that boost GABA levels in central synapses counterbalances the rectifying action of CSA on endotoxemia. 相似文献
34.
Bandar Al-Qahtani Salman Asghar Hassan Mohammad Al-Taweel Imran Jalaluddin 《Saudi Journal of Ophthalmology》2014,28(3):234-238
A 52 year old male presented with peripheral ulcerative keratitis in the right eye. Patient’s history included retinitis pigmentosa, pseudophakia (right eye), cataract (left eye), bilateral partial deafness, ischemic heart disease, hypertension, type 1 diabetes mellitus, depression, hyperparathyroidism, hypertriglycemia and renal failure. The patient was on weekly hemodialysis. The peripheral corneal ulceration remained stable until he developed sudden and rapid thinning after eight months of regular follow up and management.Laboratory investigations including immunological studies were negative and we had to rely on treatment based on clinical signs, including the visual acuity, size, depth and staining of the ulcer and perilimbal, episcleral, scleral, corneal and anterior chamber reactions. The patient was treated with medical and conservative approaches and the eye was protected with a plastic shield to avoid injury. Despite our efforts, the patient perforated his eye due to a trivial trauma during sleep. He was managed successfully with cyanoacrylate glue and a bandage contact lens. The anterior chamber reformed after the perforation was sealed and the patient is on a regular follow up with a multidisciplinary approach. 相似文献
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37.
王春生 《实用临床医药杂志》2012,16(9):18-20
目的探讨猪抗淋巴细胞免疫球蛋白与环孢素联合应用于治疗重型再生障碍性贫血(再障)的临床疗效及临床转归。方法 50例重型再障患者作为研究资料,治疗组给予猪抗淋巴细胞免疫球蛋白与环孢素联合治疗,对照组给予猪抗淋巴细胞免疫球蛋白治疗,观察并对比两组患者疗效、起效时间以及不良反应。结果治疗组总有效率明显高于治疗组,基本治愈率、明显缓解率以及有所改善率均高于对照组。经过治疗后两组患者白细胞(WBC)、血红蛋白(HGB)以及血小板(PLT)均明显升高,但治疗后治疗组WBC、HGB以及PLT均明显高于对照组。治疗组平均起效时间、牙龈增生出现例数明显高于对照组,另出现5例手颤,3例继发性糖尿病,而对照组未发现此类不良反应。结论猪抗淋巴细胞免疫球蛋白与环孢素联合应用于治疗重型再障疗效优于单用猪抗淋巴细胞免疫球蛋白治疗,但不良反应较单用猪抗淋巴细胞免疫球蛋白治疗更多,可以推荐应用,如何防治并发症仍值得思考。 相似文献
38.
Laurent Monassier Estelle Ayme‐Dietrich Gaëlle Aubertin‐Kirch Atul Pathak 《Fundamental & clinical pharmacology》2016,30(2):191-193
The mitochondrial permeability transition (mPTP) is a key feature of cardiac cell death in ischaemia‐reperfusion injury (I/R). The mPTP blocker, cyclosporine A (CsA), has been shown to give protection against reperfusion‐induced myocardial necrosis and troubles generated by acute coronary artery repermeabilization. Nevertheless, the results of the CIRCUS trial (Does Cyclosporine Improve Clinical Outcome in ST‐Elevation Myocardial Infarction Patients) seem to go against this hypothesis. Pharmacological reasons linked to CsA pharmacokinetics and pharmacodynamics could be suggested. First, it could be explained by a limited diffusion of the drug in the area at risk, due to the only inclusion of patients with a TIMI 0 or 1 coronary blood flow in the anterior territory and the absence of collateral perfusion. Second, to explain a low tissue diffusion of the compound, blood cell capture and high metabolism could be suggested. Moreover, CsA is highly metabolized by cytochrome P450 3A4 (CYP3A4), a polymorphic enzyme leading to variations of Cmax and AUC between 10–20% in patients using CsA. Finally, CsA blocks calcineurin, a protein implied in I/R damage but calcineurin inhibition could contribute to protection towards I/R damage only when Rcan1, a calcineurin natural inhibitor, expression is low. The results of the CIRCUS trial are disappointing and could contribute to the withdrawal of the mPTP blockade pharmacological strategy as a way to protect the myocardium from I/R lesions. Nevertheless, many pharmacological insights could have contributed to an increased variability and, as a consequence, an important reduction of the pharmacological power of the study. 相似文献
39.
Moo‐Kon Song Joo‐Seop Chung Young‐Don Joo Yang‐Soo Kim Sung‐Hyun Kim Young‐Mi Seol Ho‐Jin Shin Young‐Jin Choi Goon‐Jae Cho 《European journal of haematology》2009,83(1):72-78
Immunosuppressive therapy (IST) has provided an alternative treatment option for cure of aplastic anemia patients who cannot receive bone marrow transplantation. Although there have been many recent studies on the efficacy of antithymoglobulin (ATG) combined with cyclosporine A (CsA), there is no data on the correlation between the variability of CsA levels and the response to IST. Therefore, we retrospectively assessed the factors associated with IST efficacy in patients with acquired severe aplastic anemia (SAA). Sixty‐six patients were treated with ATG combined with CsA for 6 months. In the response group, the CsA levels were increased rapidly to more than 200 ng/mL within the first 2 wk after starting the IST. However, the non‐response group had a pattern of slower increase of the CsA levels. The CsA levels, during the first and second week of treatment with IST, were significantly different in the responders and non‐responders. The factors predictive of response to IST and survival were analyzed. The univariate analysis showed that a younger age at the initiation of IST, a high absolute neutrophil count prior to starting IST, a short interval between the diagnosis and initiation of IST, and high CsA levels during the first and second week of IST treatment were positively associated with the response rate and overall survival. The multivariate analysis showed that these four factors were independent factors associated with a longer patient survival. A high response rate was associated with a short interval between diagnosis and initiation of IST as well as high CsA levels during the first and second week of IST. Therefore, early intensification of CsA levels might improve patient outcome. 相似文献
40.
The field of pharmacogenomics was initiated in the 1950s and began to thrive after the completion of the human genome project 10 years ago. Thus far, more than 100 drug labels and clinical guidelines referring to pharmacogenomic biomarkers have been published, and several key pharmacogenomic markers for either drug safety or efficacy have been identified and subsequently adopted in clinical practice as pre-treatment genetic tests. However, a tremendous variation of genetic backgrounds exists between different ethnic groups. The application of pharmacogenomics in the Chinese population is still a long way off, since the published guidelines issued by the organizations such as US Food and Drug Administration require further confirmation in the Chinese population. This review highlights important pharmacogenomic discoveries in the Chinese population and compares the Chinese population with other nations regarding the pharmacogenomics of five most commonly used drugs, ie, tacrolimus, cyclosporine A, warfarin, cyclophosphamide and azathioprine. 相似文献