利福喷丁对小鼠肝微粒体药酶的诱导作用

连续给小鼠口服利福喷丁40mg/kg或20mg/kg14日后,用药鼠的戊巴比妥钠催眠时间显著缩短,利福喷丁血浓下降,鼠肝重增加,而SGPT活性无改变。鼠肝细胞中细胞色素P-450和细胞色素B_b含量明显增加,表明利福喷丁有诱导小鼠肝药酶的作用。     

月桂酸二乙醇酰胺修饰利福喷丁脂质体的制备、性质及肺部给药

目的制备表面活性剂修饰利福喷丁(RIF)脂质体，进行该脂质体水化性能、载药量、释药速度和肺部给药研究。方法采用薄膜超声法制备利福喷丁脂质体，比较月桂酸二乙醇酰胺(LDEA)，Tween 80和azone修饰利福喷丁脂质体的形态、包封率、释药速度和离体猪肺膜透过性，通过纤支镜进行肺部给药研究。结果RIF-LDEA脂质体粒径在15～50 nm，包封率为83.0%，表观透膜系数Kp为44.29；LD₅₀为675 mg·kg^-1。结论LDEA修饰使利福喷丁脂质体的载药量增加1倍、释药速度的可调性强及安全性好。经纤支镜介导灌注给药治疗肺内膜结核的效果显著。     

利福喷丁对氨茶碱药代动力学的影响

本文应用紫外分光光度法对两组家兔分别单服氨茶碱及氨茶碱加服利福喷丁后的药代动力学参数进行了对比。结果表明,按8mg/kg的剂量连服利福喷丁4d可使氨茶碱的消除速率常数(K)升高;半衰期(t_(1/2))下降;曲线下面积(AUC)减小。经统计学处理p<0.05。提示在临床上两药同服时,应加强对氨茶碱的血药浓度监测,进行个体化给药以控制氨茶碱的有效血药浓度。     

利福喷丁不同给药方法治疗老年肺结核患者的临床效果比较

目的研究利福喷丁不同给药方法治疗老年肺结核患者的临床效果。方法选取60例在我院接受治疗的老年肺结核患者,随机分为观察组与对照组,两组各有患者30例。观察组患者每周1次利福喷丁治疗,对照组患者每周2次利福喷丁治疗。结果两组患者在接受治疗6个月后,观察组患者和对照组患者在治疗总有效率方面的差异无统计学意义(P>0.05)。观察组患者不良反应方面的发生率均低于对照组,数据差异具有统计学意义(P<0.05)。结论使用利福喷丁对老年肺结核患者进行治疗时,应采用1周1次的治疗方法,患者治疗效果较好,不良反应发生率较低。     

我院1997年～2000年抗结核药应用分析

目的探讨抗结核药的应用现状及发展趋势,引导临床合理用药。方法对本院1997年～2000年间应用的抗结核药的品种、金额、DDDs以及临床应用情况进行分析。结果抗结核药用药金额年平均增长率为1065％,百生肼、利福喷丁用量上升。结论加强防治与合理用药是控制结核病的有效途径。     

结核病患者服用利福平出现药物热后改用利福喷丁42例

［摘要］目的观察结核病患者服用利福平出现药物热后改用利福喷丁的效果。方法肺结核患者服用利福平出现药物热 42例,后改用利福喷丁,0.15 g,po,qd。结果40例患者改服用利福喷丁后未发热,2例患者服用利福喷丁后再度发热,两药发生交叉药物热仅4.8%（2/42）。结论利福平致药物热患者试用利福喷丁安全,未出现严重不良反应。     

利福喷丁联合左氧氟沙星治疗初治菌阳肺结核的临床研究

目的：探讨利福喷丁联合左氧氟沙星治疗初治菌阳肺结核患者的临床疗效。方法82例初治菌阳肺结核的患者随机分为对照组和治疗组,每组41例。对照组患者单纯应用利福喷丁实施治疗;治疗组患者采用利福喷丁与左氧氟沙星联合实施治疗。结果治疗组患者肺结核病情控制总有效率90.2%明显高于对照组;痰菌检测结果完全转阴时间和用药治疗总时间（7.41±1.55）d、（12.9±2.43）d明显短于对照组（11.73±3.48）d、（17.95±4.14）d;两组用药期间没有出现药物不良反应。结论应用利福喷丁与左氧氟沙星联合对初治菌阳肺结核疾病的患者实施治疗的临床效果非常明显。     

利福平和利福喷丁在抗结核治疗中疗效的临床对比研究

目的探讨利福平和利福喷丁在抗结核治疗中疗效的临床对比。方法纳入我院80例2017年3月10日至2018年6月12日收治的结核病患者。随机数字表分组,利福平治疗组采取利福平治疗,利福喷丁治疗组则采取利福喷丁治疗。比较效果。结果利福喷丁治疗组各项指标好于利福平治疗组,P <0.05。结论利福喷丁治疗结核病的效果理想。     

利福喷丁治疗结核病大剂量比标准剂量耐受性好

美国学者完成的最新一项双盲耐受性研究显示 ,应用利福喷丁 (ｒｉｆａｐｅｎｔｉｎｅ) 90 0ｍｇ(超过标准剂量30 0ｍｇ)加异烟肼每周一次口服维持治疗结核病(ＴＢ) ,安全且耐受性良好。亚特兰大疾病控制与预防中心ＴＢ治疗科的Ｂｏｃｋ博士认为 ,利福喷丁与其他抗ＴＢ药相比具有突出的优点 ,即每周只需一次用药。但在利福喷丁6 0 0ｍｇ加异烟肼 90 0ｍｇ每周一次治疗ＴＢ病的Ⅲ期临床试验中发现 ,其“不能接受”的缺点是复发率高。为进一步评估大剂量利福喷丁的安全性和耐受性 ,Ｂｏｃｋ及其同事设计了该项研究。研究人员随机将 15 0例ＨＩ…     

利福喷丁胶囊在肺结核患者体内的药物动力学观察

测定肺结核患者单剂量po利福喷丁后的血浆药物浓度,观察其药物动力学参数.12名肺结核患者单剂量po利福喷丁胶囊450mg,以利福平为内标,用高效液相色谱法测定服药后的经时血浆药物浓度,并用PKBP-N1药物动力学程序拟合处理及计算药物动力学参数.结果:利福喷丁胶囊po符合血管外给药一室开放模型,吸收与消除半衰期分别为1.59士0.35h和16.06士1.97h,达峰时间为6.10士0,76h,峰浓度为6.32士0.68μg/ml,药-时曲线下面积为141.7±21.3μg·h/ml.提示:肺结核患者po利福平喷丁胶囊的药物动力学参数与文献报道的健康志愿者无显著性差异.     

利福喷丁的临床药物动力学研究

本文报道利福喷丁正常人药物动力学研究结果，健康志愿者１０人单剂口服利福喷丁粉剂及胶囊６００ｍｇ后的体内过程均符合血管外一室模型，其血药峰浓度分别为１７．４３ｍｇ／Ｌ（粉剂）和１８．３８ｍｇ／Ｌ（胶囊），达峰时间为９，７０ｈ（粉剂和）和８．２１ｈ（胶囊），消除半衰期（ｔ１／２ｋｅ）为１９．９０ｈ（粉剂）和１９．４２ｈ（胶囊），以上各项参数经统计学处理均无明显意义，胶囊的相对生物利用度为１０４．７２％，口服该药后有少量自尿中以原形排出体外，给药后２ｈ内分别排出给药量的１１．３０％（粉剂）和１１，２９％（胶囊）。     

利福定固体分散物的制备及生物利用度测定

用溶媒法制备了利福定固体分散物。经X—射线衍射实验证明,利福定在固体分散物中呈无定形或以分子状态分散于载体中。固体分散物2小时的体外溶出量和人体生物利用度分别较原药提高了88％和21.8％。     

利福定在大鼠离体肠囊内吸收机制研究

利福定从大鼠离体肠囊粘膜侧向浆膜侧的扩散为被动扩散过程,并需要一定时间。小肠各部位的理论延滞时间平均为31.4min,直肠部位为42.2min。     

利福喷丁及其胶囊质量标准提高的研究

目的：提高利福喷丁及其胶囊的质量标准。方法：按照《中国药典》2015年版的相关规定,参考现行标准及研究文献,考察本品的性状、鉴别、有关物质及含量。结果：修订了溶解度、有关物质和含量测定色谱条件,增订了薄层色谱鉴别方法。结论：改进的标准可以更好地控制利福喷丁原料和胶囊的质量。     

An update on the use of rifapentine for tuberculosis therapy

Introduction: Tuberculosis (TB) remains rampant throughout the world, in large part due to the lengthy treatment times of current therapeutic options. Rifapentine, a rifamycin antibiotic, is currently approved for intermittent dosing in the treatment of TB. Recent animal studies have shown that more frequent administration of rifapentine could shorten treatment times, for both latent and active TB infection. However, these results were not replicated in a subsequent human clinical trial.

Areas covered: This review analyses the evidence for more frequent administration of rifapentine and the reasons for the apparent lack of efficacy in shortening treatment times in human patients. Inhaled delivery is discussed as a potential option to achieve the therapeutic effect of rifapentine by overcoming the barriers associated with oral administration of this drug. Avenues for developing an inhalable form of rifapentine are also presented.

Expert opinion: Rifapentine is a promising active pharmaceutical ingredient with potential to accelerate treatment of TB if delivered by inhaled administration. Progression of current fundamental work on inhaled anti-tubercular therapies to human clinical trials is essential for determining their role in future treatment regimens. While the ultimate goal for global TB control is a vaccine, a short and effective treatment option is equally crucial.     

国产利福喷丁治疗肺结核的临床对照研究(附三年随访结果)

以利福平为对照,全面考核利福喷丁治疗排菌肺结核的效果以及满疗程三年随访结果。560名排菌肺结核患者,其中486例为初治、74例为复治病例。全部病例随机分成Ⅰ、Ⅱ、Ⅲ甲和Ⅲ乙组。给药方案分别为1LHZE/8L_1H_2E_2、1LHZE/8L_1H_2E_2、1RHZE/8R_2H_2E_2和1RHZE/8RHE。511例满疗程。治疗结果表明:(1)所有各组在治疗的第二个月痰培养阴性的结果是相似的(P>0.05);(2)治疗完毕痰培养阴性率,初治组为98.7～100％(P>0.05),复治组93.7～100％(P>0.05);(3)利福喷丁组未见严重副作用。506例痰培养阴性病例中有456例作三年随访。402例初治病例中,细菌学和X线检查观察到有旧病复发在Ⅱ组有2例、Ⅲ乙组有1例;X线检查证实复发同时直接涂片阳性但培养测定仍为阴性的,Ⅰ组、Ⅱ组各1例。54例复治病例中,痰涂片阳性和培养阳性及X线检查证实复发和X线检查复发Ⅱ组有1例。根据上述结果作者认为国产利福喷丁是一个高效、长效、安全的抗结核药,推荐在国内推广应用。     

The canine CYP1A2 deficiency polymorphism dramatically affects the pharmacokinetics of 4-cyclohexyl-1-ethyl-7-methylpyrido[2,3-D]-pyrimidine-2-(1H)-one (YM-64227), a phosphodiesterase type 4 inhibitor.

In a previous study, it was shown that the novel canine single nucleotide polymorphism (SNP) CYP1A2 1117C>T yields an inactive enzyme. In this study, the effect that this SNP has on the pharmacokinetics of 4-cyclohexyl-1-ethyl-7-methylpyrido[2,3-d]pyrimidine-2-(1H)-one (YM-64227) was investigated. Plasma concentrations of the unchanged drug and five of its metabolites (MM-1 to MM-5) were determined after either intravenous or oral administration of YM-64227 to genotyped dogs (C/C, C/T, and T/T groups). Liver microsomes were prepared from these dogs to determine the in vitro metabolic clearance of YM-64227. After a single oral administration, the maximum plasma concentration and absolute bioavailability of YM-64227 in the T/T group were 17.1 times and 27.2 times higher than those in the C/C group, respectively, whereas the pharmacokinetics of YM-64227 after intravenous administration were not affected by genotype. The metabolic profiles in the T/T group were quite distinct from the others; i.e., the main metabolite was MM-2 in the C/C group, whereas MM-1 and MM-5 were the main metabolites in the T/T group. The formation clearances of MM-2 and MM-3 in the microsomes derived from T/T type dogs were significantly lower, whereas those of MM-1, MM-4, and MM-5 were not affected. A statistically significant correlation was observed between the in vivo and in vitro metabolic intrinsic clearances (r = 0.82, p < 0.001). The canine CYP1A2 1117C>T SNP proved to be responsible for a substantial portion of the interindividual variability in the pharmacokinetics of YM-64227.     

Pharmacokinetics of recombinant human basic fibroblast growth factor in rabbits and mice serum and rabbits aqueous humor

AIM: To study the pharmacokinetics of recombinant human basic fibroblast growth factor (rhbFGF) in rabbits and mice after iv and postocular administration, and the changes of rhbFGF in rabbits aqueous humor after postocular administration. METHODS: After iv or postocular administration three doses of rhbFGF in rabbits and mice, rhbFGF concentration in serum and rabbit aqueous humor was determined by enzyme-linked immunosorbent assay. RESULTS: Serum concentration-time data of rabbits after iv administration of rhbFGF 1, 2, and 4 μg/kg were fitted to bi-exponential equations with half-lives of 0.9, 0.9, and 0.6 min for T1/2α and 7, 8, and 4.7 min for T1/2β. Plasma concentration-time data of mice after iv administration of rhbFGF 2.5, 5 and 10 μg/kg were fitted to bi exponential equations with half-lives of 0.4, 0.6, and 0.9 min for T1/2α　and 6, 5, and 7 min for T1/2β.The AUCs were linearly correlated to doses in both cases (rrabbit=0.997, rmouse=0.999). The serum concentrations of rhbFGF were very l     

利福定不同晶型和制剂的生物利用度

利福定为一多晶型化合物。实验表明由Ⅰ型或Ⅳ型晶型的利福定制成的胶囊剂有较高的生物利用度和疗效。     

长托宁复合新斯的明用于肌松拮抗作用临床观察

目的：观察长托宁和新斯的明用于残余肌松拮抗的临床效果。方法：随机选择75例手术患者分成长托宁0．01mg／kg＋新斯的明0．02mg／kg（A组）,长托宁0．015mg／kg和新斯的明0．02mg／kg（B组）,阿托品0．01mg／kg＋新斯的明0．02mg／kg（C组）。术毕患者有轻微呼吸后分别给予上述混合药物。记录给药前（阳）,给药后2min（T1）,5min（T2）,10min（T3）,15min（T4）的MAP、HR、RPP、肌力、唾液分泌量、口干评分及不良反应。结果：3组MAP、肌力、唾液分泌量、口干评分无明显差异;HR,RPP在C组同A、B组在T1,T2,T3差异有显著性（P〈0．01）,与本组T0相比差异有显著性（P〈0．01）;B组HR在T1、T2、113与本组哟相比有明显下降（P〈0．05）。结论：长托宁0．01mg／kg＋新斯的明0．02mg／kg用于术毕拮抗残余肌松效果良好,不良作用轻微,其比例适当临床运用安全有效.