抗癌药——Eribulin甲磺酸盐

天然化合物软海绵素B在体内外表现出良好的抗癌活性，但因来源不足限制了其应用。Eribulin甲磺酸盐（E-7389，NSC-707389，曾用代号：ER-086526），是软海绵素B经结构优化后得到的一个大环酮类似物，体外试验显示其与天然的软海绵素B有相同的亚纳摩尔水平的抗癌活性。给大鼠、犬和患有顽固性或晚期实体瘤患者用药后，Eribulin甲磺酸盐能迅速、广泛地分布到体内组织中，且终末半衰期很长。Eribulin甲磺酸盐在已经过化学治疗的患有顽固性或晚期实体瘤患者身上显示了良好的抗癌活性，且与其他抗癌药物，如吉西他滨、顺铂、表柔比星、曲妥单抗、多西紫杉醇、长春瑞滨联用时能产生协同作用。     

Azilect获得欧盟最终批准

Teva制药公司和Lundbeck公司的单胺氧化酶B抑制剂Azilect(rasagiline，雷沙吉兰)(I)获准最终欧盟批准，作为早期帕金森病(PD)患者的单药治疗和中至重度PD患者的辅助治疗。     

欧委会暂停罗氏抗HIV药物奈非那韦在欧盟的销售许可

罗氏制药公司于2007-06将其抗HIV药物奈非那韦(viracept)从欧盟市场撤出,并声称该药的销售许可因正在接受当局的审查而暂停。欧委会于2007-08-04宣布暂     

二甲双胍降糖疗效的综合评价

二甲双胍降糖机制全面,无论单药或联合用药,均能有效降低血糖,全面降低空腹血糖、餐后血糖和糖化血红蛋白。除降糖作用外,二甲双胍还对其他器官及疾病有一定的临床作用,有很好地应用前景。本文通过查阅国内外文献,对二甲双胍降糖疗效进行综合评价。     

帕金森病治疗新药——雷沙吉兰

雷沙吉兰是由Lundbeck公司和Teva公司联合开发的帕金森病（PD）治疗药物，系一种新颖、有效的第2代选择性单胺氧化酶B（MAO-B）抑制剂。该药于2005年1月第1次获准在以色列上市，随后于2005年2月获欧盟批准，2005年6月首次在欧盟国家英国上市，并已获得FDA的可批准函。此外，该药目前还在进行用于治疗老年痴呆（AD）、抑郁症、儿童多动症的临床研究。     

04025 Zelapar离被批准更近了一步

Valeant制药公司称，在其成功完成美国FDA最终批准Zelapar(selegiline，司来吉兰)(Ⅰ)要求的两项安全性研究后，已向FDA递交了一份对(Ⅰ)的可批准函的完全回应。他们预期可以于2005年中期上市(Ⅰ)。     

不同剂量及给药方式的甲氨喋呤治疗宫外孕临床疗效分析

近10余年来，宫外孕的发生率较前明显增加，成为妇产科常见急腹症之一；同时随着诊疗技术的进步，宫外孕的早期诊断率也较前大为提高。宫外孕的药物治疗可免除手术，保留输卵管的完整结构和功能，在早期宫外孕的治疗中越来越重要。现将我院应用不同剂量不同给药方式甲氨喋呤治疗的早期宫外孕225例临床疗效及副作用作出分析。     

欧盟批准维格列汀可单药治疗不能服用盐酸甲福明的2型糖尿病患者

2012年2月,欧盟委员会批准Novartis公司的二肽基肽酶-4抑制剂维格列汀（vildagl;ptin／Gatvus）可单药治疗不能服用盐酸甲福明（metforminhydrochIoride）的2型糖尿病患者。2型糖尿病患者中近1／4因不能耐受或存在肾损害等禁忌证而不能服用现标准降血糖药物盐酸甲福明,而维格列汀能为这类患者提供～种有效且耐受性很好的替代治疗选择,临床意义重大。     

米非司酮联合甲氨蝶硷和中药治疗异位妊娠60例临床观察

近年来异位妊娠发病率呈上升趋势,有报道发病率增加6倍,约占所有妊娠的2%[1].随着B超技术的提高,临床上80%的异位妊娠得到早期诊断.所以保守治疗的必要性和可行性备受关注.现将我院2005年1月至2007年6月应用米非司酮联合甲氨蝶砱和中药治疗异位妊娠60例临床分析报道如下.……     

单剂量肌肉注射甲氨喋呤治疗异位妊娠的药物动力学

目的 研究单剂量肌注甲氨喋呤(MTX)治疗异位妊娠(EP)的药动学特点,并计算其参数.方法 给予9例输卵管异位妊娠患者im MTX(1 mg·kg-1),分别于给药0-24 h内多点采静脉血,用荧光偏振免疫法测定MTX的浓度,用3p97软件计算药动学参数.结果 MTX的药动学符合一级吸收的二室模型.结论 单剂肌注MTX的药动学研究有助于深入分析EP治疗成功与否的相关因素.     

Evaluation of different substrates for inkjet printing of rasagiline mesylate

The main goal of the present study was to evaluate applicability of the different model substrates, namely orodispersible films (ODFs), porous copy paper sheets, and water impermeable transparency films (TFs) in preparation of the inkjet-printed drug-delivery systems. Rasagiline mesylate (RM) was used as a low-dose active pharmaceutical ingredient (API). Flexible doses of the drug in a single unit were obtained by printing several subsequent layers on top of the already printed ones, using an off-the-shelf consumer thermal inkjet (TIJ) printer. The produced drug-delivery systems were subjected to microscopic and chemical analysis together with solid-state characterization and content uniformity studies. The results revealed that RM recrystallized on the surface of ODFs and TFs, and the printed crystals were arranged in lines. No drug crystals were detected after printing on the surface of the copy paper due to absorption of the ink into the matrix of the substrate. The best linear correlation between the dose of the drug and the number of the printing layers was obtained for the porous copy paper. The other two substrates showed poor linearity and unacceptable standard deviations of the printed drug substance due to limited absorption of the API ink into the carrier. The shear stress between the substrate, the print head, and the paper feeding rollers caused smearing of the drug that had been surface-deposited during the earlier printing cycles. In conclusion, this study indicates that the edible substrates with absorption properties similar to copy paper are favorable for successful preparation of drug-delivery systems by TIJ printers.     

Nasal in-situ gels for delivery of rasagiline mesylate: improvement in bioavailability and brain localization

Abstract

Intranasal thermosensitive gel for rasagiline mesylate (RM) was developed for effective treatment of Parkinson’s disease. Intranasal gels were prepared by combination of poloxamer 407 and poloxamer 188 (1:1) with mucoadhesive polymers (carbopol 934?P and chitosan). The formulations were evaluated for sol–gel transition temperature, in-vitro drug release and in-vivo mucociliary transit time. Further, optimal intranasal gel formulations were tested for in-vivo pharmacokinetic behavior, nasal toxicity studies and brain uptake studies. It was found that optimal formulations had acceptable gelation temperature (28–33?°C) and adequate in-vitro drug release profile. Pharmacokinetic study in rabbits showed significant (p?<?0.05) improvement in bioavailability (four- to six-folds) of the drug from intranasal gels than oral solution. Chronic exposure studies in Wistar rats showed that these intranasal gels were non-irritant and non-toxic to rat nasal mucosa. Estimation of RM in rat brain tissue showed significant (p?<?0.01) improvement in uptake of RM form intranasal gel formulations than nasal solution.     

LC-MS/MS法测定人血浆中甲磺酸雷沙吉兰的浓度及其体内药动学研究

目的建立人血浆中甲磺酸雷沙吉兰(rasagiline mesylate,PAI)的液相色谱-串联质谱(LC-MS/MS)测定方法,并应用于研究其在中国健康人体内的药动学特征。方法以氯吡格雷为内标,血浆样品经液-液萃取后,通过三重四级杆串联质谱仪,以选择性正离子反应监测进行测定,检测离子对为m/z172.3→117.1(雷沙吉兰),m/z322.3→184.0(氯吡格雷)。甲磺酸雷沙吉兰线性范围为0.1047~20.93μg·L-1,定量限为0.1047μg·L-1,方法学各项指标均符合要求。应用此法研究24名(男女各半)中国健康志愿者口服甲磺酸雷沙吉兰片的药动学特点及进行了统计学比较。结果结果显示0.5、1.0及2.0 mg 3个剂量组(n=12)甲磺酸雷沙吉兰的吸收呈线性动力学特征;中剂量多次给药后,无蓄积现象;性别对雷沙吉兰主要药动学参数的影响差异也无统计学意义;但高脂饮食对雷沙吉兰的药物峰浓度有明显影响,但对吸收程度无明显影响。结论建立的LC-MS/MS测定法专属、灵敏,满足甲磺酸雷沙吉兰片的人体药动学研究。     

Development and validation of a reverse phase liquid chromatography method for the quantification of rasagiline mesylate in biodegradable PLGA microspheres

In the present study, a reverse phase high performance liquid chromatographic method was developed and validated for the determination of rasagiline mesylate in biodegradable microspheres. Chromatographic separation was carried out on a RP-18 column using a mobile phase consisting of acetonitrile:water (5:95, v/v) adjusted at pH 3.1. Flow rate was 1.0 ml min⁻¹ and UV detection at 290 nm. Acyclovir was used as the internal standard. The calibration curve was linear over the range 0.5–20.0 μg ml⁻¹. R.S.D. for precision was <1.8%. Accuracy ranged between 99.01% and 102.55% with a R.S.D. lower than 1.3%. LOD and LOQ were 0.07 μg ml⁻¹ and 0.23 μg ml⁻¹, respectively. The method was simple, rapid, and easy to apply, making it very suitable for routine analysis of rasagiline mesylate in biodegradable PLGA microspheres. It could be also used with reliability for the determination of the drug in other pharmaceutical dosage forms.     

Spotlight on rasagiline in Parkinson's disease

Rasagiline (Azilect) is a novel, selective, irreversible second-generation inhibitor of monoamine oxidase type B (MAO-B). It is administered orally once daily and is approved in the US, Canada, Mexico, Israel and the EU for use as monotherapy and as adjunct therapy in the treatment of Parkinson's disease. Results of well designed clinical studies indicate that rasagiline is effective as initial monotherapy and improves Parkinson's symptomatology in patients with early Parkinson's disease. In addition, when administered in conjunction with levodopa, in patients with moderate to advanced disease and motor fluctuations, rasagiline reduces mean daily 'off' time and increases daily 'on' time without troublesome dyskinesias, compared with controls. Rasagiline is generally well tolerated as monotherapy and adjunctive therapy and is administered once daily. Thus, rasagiline, administered as a simple and convenient dosage regimen, is a well tolerated and effective option for monotherapy in patients with early Parkinson's disease and for adjunctive therapy in patients with moderate to advanced disease.     

洛美他派甲磺酸盐

Aegerion’s公司研制开发的洛美他派(lomitapide)甲磺酸盐于2012年12月21日由美国FDA批准在美国上市,商品名为Juxtapid。该药为胶囊剂,用于治疗纯合子家族性高胆固醇血症(HoFH)。该药获准与低脂饮食和其他降脂药物一起使用治疗HoFH,可降低患者的低密度脂蛋白胆固醇、总胆固醇、载脂蛋白B和非高密度脂蛋白     

Safety of rasagiline for the treatment of Parkinson's disease

INTRODUCTION: Levodopa remains the gold standard treatment for Parkinson's disease (PD), but chronic treatment induces motor fluctuations and dyskinesias. Other dopaminergic agents, such as dopamine agonists, catechol-O-methyl transferase inhibitors and monoamine oxidase B enzyme inhibitors (MAO-B I) have also been developed to treat patients with PD. Rasagiline is a second generation MAO-B I inducing moderate symptomatic and possibly disease-modifying benefits with apparently good tolerability and safety profile in PD patients. AREAS COVERED: The safety of rasagiline in early or advanced PD is discussed. Details about clinical trial data, post hoc analysis in the elderly or regarding cognitive or behavioral effects, food-drug interactions and effects on levodopa-induced dyskinesias are given. EXPERT OPINION: Rasagiline is effective and well tolerated in PD as monotherapy or in combination with levodopa. There was no evidence of a difference in tolerability between younger or older PD patients included in published trials. Food interactions studies with tyramine did not provide evidence of clinical concerns. Drug interaction should be monitored. The risk of serotonin toxicity with serotoninergic antidepressants remains insufficiently characterized, while current available data in small groups of subjects suggest a low risk.     

Nelfinavir mesylate

Nelfinavir is an inhibitor of the HIV-1 and HIV-2 protease, with good in vivo activity in HIV-infected patients. Nelfinavir is used in combination with other antiretroviral medications as part of a potent antiretroviral regimen. When used in this manner, 50-75% of patients who are na?ve to antiretroviral therapy have plasma HIV RNA levels below the limit of detection (< 400 copies) after 12 months of treatment. This use of nelfinavir in combination regimens is associated with an increase of almost 200/mm3 CD4+ lymphocytes at 12 months of therapy. Initial trials and clinical experience indicate that nelfinavir is equipotent to other potent protease inhibitors (PIs). The drug is well-tolerated, with mild diarrhoea being the most common side effect in 12-20% of patients. Virologic failure of nelfinavir is associated with genotypic and phenotypic changes that have a unique pattern that may retain susceptibility to other PIs. The results of small, non-controlled trials suggest these failures can be rescued with a second protease-based regimen. Due to the above characteristics, nelfinavir has become the most frequently prescribed first line PI.