Comparison of Chinese and Western rifapentines and improvement of bioavailability by prior taking of various meals

Bioavailability was measured by rifapentine (RPE) serum concentrations and by the urinary ratio between RPE and creatinine, in specimens obtained 4-50 h after 600 mg RPE preceded by food. The bioavailabilities of RPEs manufactured in China and by a Western manufacturer were similar after a standard English breakfast, and serum concentrations were also similar to those obtained in an earlier Italian study following a complex meal. Although absorption of RPE was unsatisfactory after lipid-rich biscuits or shortbread, absorption after egges and toast was excellent and was nearly as good after a fast-food sandwich. The urinary measure of bioavailability at 26 h appeared as efficient as peak serum estimations at 6, 8 and 26 h. Fast-food sandwiches are being taken before RPE in a current clinical trial of Chinese RPE in Hong Kong.     

利福布汀联合多种药物长效治疗耐多药肺结核疗效观察

目的:评价利福布汀联合多种药物长效治疗耐多药肺结核的临床疗效与安全性。方法:86例耐多药肺结核患者随机分为对照组和观察组各43例。两组患者均给予左氧氟沙星和帕司烟肼及乙胺丁醇、丙硫异烟胺、阿米卡星等药物治疗;同时对照组加用利福喷汀;观察组加用利福布汀。均连续治疗18个月后,比较两组患者痰液涂片及痰结核分枝杆菌培养阴转率、X线胸片病灶吸收率和空洞闭合率,以及药品不良反应发生情况。结果:观察组临床痰液涂片和痰结核分枝杆菌培养阴转率分别为41.86%、32.56%,与对照组相当(P>0.05)。两组X线胸片病灶吸收率、空洞闭合率、药品不良反应发生率等比较,差异无统计学意义(P>0.05)。结论:耐多药肺结核患者采用利福喷汀或利福布汀联合多种药物长效治疗均可加速患者痰液细菌学转阴和病灶吸收及空洞闭合,同时具有较高安全性。     

百生肼和利福喷汀治疗复治涂阳肺结核的疗效分析

目的：评价百生肼、利福喷汀治疗复治涂阳肺结核的疗效。方法选取本科2005-2011年收治的复治涂阳肺结核患者60例,以异烟肼、利福平、乙胺丁醇、吡嗪酰胺和链霉素治疗为标准组,以百生肼、利福喷汀、乙胺丁醇、吡嗪酰胺和链霉素治疗为非标准组。观察两组治疗后痰菌阴转率和病灶吸收总有效率情况。结果治疗2、5、8月末痰菌阴转,标准组分别为10例（33.3%）、13例（43.3%）、16例（53.3%）;而非标准组为18例（60.0%）、22例（73.3%）、26例（86.7%）,两组比较差异有统计学意义（P ＜0.05）。疗程结束后,X 线胸片吸收情况,标准组总有效率63.3%（19/30）,非标准组总有效率86.7%（26/30）,两组比较差异有统计学意义（ P ＜0.05）。结论百生肼、利福喷汀治疗复治涂阳肺结核,痰菌阴转率和病灶吸收总有效率较优。     

Determination of rifampicin and its main metabolite in plasma and urine in presence of pyrazinamide and isoniazid by HPLC method

A reversed phase HPLC method is described for the simultaneous estimation of rifampicin and its major metabolite desacetyl rifampicin, in the presence of isoniazid and pyrazinamide, in human plasma and urine. The assay involves simple liquid extraction of drug, metabolite and internal standard (rifapentine) from biological specimens and their subsequent separation on a C₁₈ reversed phase column and single wavelength UV detection. In plasma as well as in urine samples, all the three compounds of interest eluted within 17 min. Using methanol–sodium phosphate buffer (pH 5.2; 0.01 M) (65:35, v/v) as mobile phase under isocratic conditions, it was established that isoniazid, pyrazinamide and ascorbic acid (added to prevent oxidative degradation of analytes) did not interfere with the analyte peaks. Recoveries (extraction efficiency) for drug were greater than 90% in both plasma and urine, whereas for metabolite the values were found to be 79 and 86% in plasma and urine, respectively. The plasma and urine methods were precise (total coefficient of variation ranged from 5 to 23%) and accurate (−7 to 5% of the nominal values) for both the analytes. Individual variance components, their estimates and their contribution to the total variance were also determined. Using the same method, unknown samples supplied by WHO were assayed and good correlations were obtained between the found and intended values. The method developed proved to be suitable for simultaneous estimation of rifampicin and desacetyl rifampicin in plasma and urine samples.     

利福喷丁和苯巴比妥诱导小鼠肝细胞滑面内质网增生的作用

利福喷丁是新型长效抗结核抗生素,通过透射电镜观察,发现它和典型的肝微粒体酶诱导剂苯巴比妥均能显著诱导小鼠肝细胞滑面内质网的增生。由于这种作用常与肝微粒体酶诱导作用有关,故本文从形态学方面证实了利福喷丁和苯巴比妥对肝微粒体酶具有诱导作用。     

利福喷丁与利福平治疗肺结核的Meta分析

目的:评价利福喷丁与利福平治疗肺结核的疗效及安全性.方法:搜集公开发表的有关利福喷丁与利福平治疗肺结核的随机对照临床试验,按照Meta分析方法,运用Rev Man4.2.10软件对符合条件的纳入文献进行分析.结果:纳入文献13篇,总样本量2294例,利福喷丁治疗组1171例,其中,痰菌转阴1118例,病灶吸收1147倒,空洞闭合393例;利福平治疗组1123例,其中,痰菌转阴1044例,病灶吸收1024例,空洞闭合335例.痰菌转阴、空洞闭合的疗效指标合并OR值分别为1.67,1.48(P＜0.01),病灶吸收疗效指标合并OR值为1.43(P＞0.05).结论:与利福平治疗肺结核病相比,利福喷丁在促进痰菌转阴、空洞闭合方面疗效更显著,但在促进病灶吸收方面疗效差异无统计学意义.     

利福布丁较利福喷丁治疗耐多药肺结核的系统评价

目的评价利福布丁较利福喷丁治疗耐多药肺结核的有效性和安全性。方法计算机检索Medline、the Cochrane Cen-tral Register of Controlled Trials(CENTRAL)、CBM、CNKI、万方学位论文和会议数据库,Clinical trial.gov。检索日期截止至2008年10月。纳入利福布丁较利福喷丁治疗耐多药肺结核的随机对照试验。结果共纳入1个随机对照试验,完成治疗分析的和意向性治疗分析均表明在不同治疗阶段,利福布丁和利福喷汀两组病人痰菌阴转率、病灶显效率、病灶有效率比较,差异均无统计意义(p>0.05)。利福布丁和利福喷汀两组病人满疗程时空洞闭合率、不良事件发生率、肝损害发生率及严重不良事件发生率比较,差异也无统计学意义(p>0.05)。结论一个试验提示,利福布丁与利福喷丁治疗耐多药肺结核的疗效可能相似。需进一步开展随机、双盲、对照试验来确认两药对耐多药肺结核的相对效果。     

三种利福霉素类抗痨药物耐药状况对比分析

目的探讨三种利福霉素类抗痨药物的耐药状况。方法采用鸡蛋固体培养基对168例肺结核患者进行痰结核菌培养,对培养阳性菌株采用绝对浓度间接法对国产利福平、进口利福平及利福喷丁进行耐药检测,以50μg/ml为耐药界限。结果共获得结核分支杆菌54株,其中耐国产利福平者31株,耐进口利福平者36株,耐利喷丁者10株,耐药率分别为57.4%,66.7%和18.5%。利福喷丁耐药率明显低于国产利福平(χ2=17.3382,P<0.0001)和进口利福平(χ2=25.5989,P<0.0001),而国产利福平和进口利福平耐药率无差别(χ2=0.9829,P>0.05)。结论国产利福平和进口利福平耐药状况均非常严重,因此,在临床用药过程中,对国产利福平耐药者不宜以进口利福平代替,而应以利福喷丁替代以保证疗效。     

利福喷丁不同给药方法治疗老年肺结核临床疗效研究

目的探讨利福喷丁不同给药方法在老年肺结核患者中的临床治疗效果。方法选择2009年6月-2010年6月在湖南省结核病医院进行治疗的老年肺结核患者86例,随机分为两组,分别采取利福喷丁1次／周与利福喷丁2次倜方法进行治疗,观察两种方法的治疗效果。结果利福喷丁1次／周治疗组的总有效率为93．02％、利福喷丁2次／周治疗组总有效率为95．35％,两组相比差异无统计学意义（P〉0．05）;利福喷丁2次／周治疗组药物不良反应比例显著高于利福喷丁1次／周治疗组。结论利福喷丁1次／周治疗方案,在老年人结核病的治疗中不但可以起到良好的治疗效果,还可以有效地降低不良反应的发生。     

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）。