利福喷汀治疗耐利福平肺结核的疗效分析

目的分析增加利福喷汀的用药剂量对利福平耐药肺结核的疗效，以评价利福喷汀在治疗利福平耐药患者中的作用。方法根据药敏结果选取耐利福平肺结核患者101例，分为治疗1组（利福平低耐），治疗2组（利福平高耐），两组治疗方案中均含利福喷汀，对照组（利福平高耐）治疗方案中不合利福喷汀。观察治疗后3、18个月疗效。结果治疗1组在各阶段的痰菌阴转率、病灶吸收和空洞闭和情况明显优于治疗2组和对照组，两组差异有统计学意义；治疗2组的痰菌阴转率、病灶吸收和空洞闭和情况略优于对照组，两者差异无统计学意义。结论对利福平耐药的患者尤其在利福平低度耐药病例中，可以选择增加利福喷汀用药剂量的方案进行治疗，在利福平高度耐药病例中利福喷汀的作用不能确定。     

异烟肼、利福平治疗肺结核致肝毒性易感基因的研究

目的：探讨N-乙酰基转移酶(NAT2)基因型与异烟肼、利福平治疗肺结核致肝毒性的相关性。方法：通过聚合酶链反应-限制性片段长度多态性(PCR—RFLP)技术分析67例经利福平、异烟肼治疗后发生或未发生肝功能异常的肺结核患者NAT2基因多态性的部位、性质及发生率。结果：病例组和对照组857位密码子多态性分别是20．3％和7．1％，两组差异显著。结论：NAT2基因型与异烟肼和利福平所致肝毒性关系密切，其中857位密码子点突变可能是结核患者发生肝毒性的易感基因型之一。     

毛细管气相色谱柱顶空进样法测定利福平及氯诺昔康中有机溶剂残留量

 目的测定利福平及氯诺昔康中有机溶剂残留量。方法毛细管气相色谱柱顶空进样法，FID检测器。利福平以5%苯基甲基聚硅氧烷为固定相，柱温50℃；氯诺昔康以聚乙二醇为固定相，柱温50℃维持15min,以10℃·min^-1的速率升温至165℃,维持5min。结果甲醇、丙酮、氯仿、正丁醇线性关系r分别为0.9999，0.9999，0.9984，0.9998;平均回收率分别为96.0%，97.3%，81.1%，93.9%,RSD分别为2.7%，1.9%，8.8%，2.5%(n=5)。结论方法柱效高、灵敏、准确，适用于利福平及氯诺昔康中有机溶剂残留量测定。     

水飞蓟宾胶囊对异烟肼和利福平肝损害小鼠的保护作用

目的：观察水飞蓟宾胶囊(SC)对异烟肼(INH)与利相干(RFP)合用致肝损伤小鼠的保护作用。方法：测定肝损伤小鼠在给予SC后肝指数、血清谷丙转氨酶(ALT)的活性，肝匀浆中谷胱甘肽(GSH)及丙二醛(MDA)的含量，肝微粒体中细胞色素P450含量及其亚型2E1的活性。结果：SC可对抗INH和RFP合用引起的肝指数、血清ALT水平、肝匀浆中的MDS含量及P450、4502E1活性的升高，增加GSH含量；病理学检查SC能明显减轻肝细胞的变性和坏死。结论：SC对INH和RFP肝毒性的保护作用与其稳定肝细胞膜、抑制脂质过氧化反应、清除自由基、抑制药物代谢酶有关。     

对贵刊刊登《利福平(0.1%)液治疗慢性化脓性中耳炎》的验证

贵刊1999年18卷4期225页刊登的"利福平(0.1 %)液治疗慢性化脓性中耳炎"一文[1],笔者阅后很受启发,并在临床实践中进行验证,现将38例结果报道如下.     

Chemo-Radiotherapy in Locally Advanced Squamous Cell Carcinoma of the Head and Neck: Factors Affecting Toxicity Patterns

Abstract

Radiation and chemotherapy in the treatment of locally advanced squamous carcinoma of the head and neck can be used according to different strategies: concomitant, alternation, consecutive. The limiting acute toxicity is local with the radiosensitizing capacity of the drug and type of radiation fractionation being the predominant factors. Regimens providing more that 50% of complete responses are usually associate with a more than 40% incidence of severe local reaction. More information is needed on late toxicity that influences the quality of life for these patients.     

Treatment of pruritus of primary biliary cirrhosis with rifampin

Pruritus can be a debilitating symptom in patients with chronic cholestasis. Based on previous reports of its efficacy, we evaluated the impact of rifampin on the pruritus associated with primary biliary cirrhosis. Fourteen patients were included in a randomized, crossover study. After a 15-day washout period, subjects were followed for three weeks. During the first and third week, patients received 600 mg of rifampin or placebo; no treatment was administered during the second week. Pruritus was subjectively scored on a scale from 0 to 100. With rifampin, pruritus disappeared in 11 patients and partially improved in three; with placebo, only two had a partial response (P<0.001). Six patients with a prior poor or no response to cholestyramine improved with rifampin. No changes in biochemical tests or side effects were observed during this period. We conclude that short-term administration of rifampin relieves pruritus in primary biliary cirrhosis. When administered over a period of eight months in an open study, the relief of pruritus was maintained, while one individual developed an allergic reaction. Rifampin appears to be a safe drug in the management of the pruritus of primary biliary cirrhosis.     

Two cases of tuberculous retropharyngeal abscess in adults

Retropharyngeal abscess (RPA) is an acute or chronic deep neck tissue infection. Tuberculous RPA is chronic and extremely rare in adults. A 20-year-old female patient visited the local hospital due to cough and sputum. The sputum smear was positive for acid-fast staining, and lung computed tomography (CT) indicated pulmonary tuberculosis (TB). The patient received the standard regimen of isoniazid+rifampicin+pyrazinamide+ethambutol (HRZE) for 6 months. After HRZE, pulmonary symptoms improved, but some pharyngeal discomfort remained. In another case, a 25-year-old male patient was admitted to our hospital because of a mass on the left side of his neck. Lymph node TB was considered after a puncture biopsy. Lung CT showed no obvious abnormality. After HRZE for 5 months, the mass had progressively enlarged. Both patients underwent B-ultrasonography-guided puncture, and Xpert® MTB/RIF of the abscess was positive and rifampin-sensitive. Tuberculous RPA was diagnosed and treated with isoniazid+rifampicin (HR) for 12 months. After combination anti-TB therapy and surgical drainage, both patients fully recovered. Tuberculous RPA is rare in adults; because of pharyngeal symptoms or progressive enlargement of a neck mass with anti-TB treatment, clinicians need to suspect tuberculous RPA in adults, which is treated with anti-TB therapy and surgery.     

A Physiologically Based Pharmacokinetic Modeling Approach to Predict Drug-Drug Interactions of Buprenorphine After Subcutaneous Administration of CAM2038 With Perpetrators of CYP3A4

CAM2038, FluidCrystal injection depot, is an extended release formulation of buprenorphine given subcutaneously every 1 week (Q1W) or every 4 weeks (Q4W). The purpose of this research was to predict the magnitude of drug-drug interaction (DDI) after coadministration of a strong CYP3A4 inducer or inhibitor using physiologically based pharmacokinetic (PBPK) modeling. A PBPK model was developed for CAM2038 based on the previously published buprenorphine PBPK model after intravenous and sublingual administration and the PK profiles after subcutaneous administration of CAM2038 from 2 phase I clinical trials. The strong CYP3A4 inhibitor ketoconazole was predicted to increase the buprenorphine exposure by 35% for the Q1W formulation and 34% for Q4W formulation, respectively. Also, the strong CYP3A4 inducer rifampin was predicted to decrease the buprenorphine exposure by 26% for both the Q1W and Q4W formulations. The results provided insight into the potential DDI effect for CAM2038 and suggested a lack of clinically meaningful DDI when CAM2038 is coadministered with CYP3A4 inhibitor or inducer. Therefore, no dose adjustment is required when CAM2038 is coadministered with CYP3A4 perpetrators.