小剂量红霉素联合孟鲁司特钠治疗儿童哮喘临床疗效

目的：研究小剂量红霉素联合孟鲁司特钠治疗儿童哮喘的临床疗效。方法：选取河南科技大学第一附属医院2020年1月至2022年6月诊治的90例哮喘患儿,采用随机对照方法分为观察组和对照组,各45例。对照组采用孟鲁司特钠治疗,观察组采用小剂量红霉素联合孟鲁司特钠治疗,比较两组患儿疗效、并发症、肺功能、儿童哮喘控制测试(C–ACT)评分、血清炎症因子及T淋巴细胞的差异。结果：观察组患儿治疗总有效率高于对照组,差异具有统计学意义(P <0.05);观察组患儿消化道症状、肝肾功能损伤、嗜睡及心率失常发生率高于对照组,但差异无统计学意义(P> 0.05);观察组患儿治疗后用力肺活量(FVC)、第1秒用力呼气量(FEV1)、呼气流量峰值(PEF)及C–ACT评分均高于对照组,差异具有统计学意义(P <0.05);观察组患儿治疗后血清白三烯D4(LTD4)及肿瘤坏死因子–α(TNF–α)、CD3⁺、CD4⁺及CD8⁺均低于对照组,差异具有统计学意义(P <0.05)。结论：小剂量红霉素联合孟鲁司特钠可改善哮喘患儿肺功...     

HPLC测定复方依托红霉素洗剂中依托红霉素的含量

目的：建立复方依托红霉素洗剂中依托红霉素的含量测定方法。方法：采用高效液相色谱法，色谱柱为Kro-masil C18柱（4．6mm×250mm，5μm），流动相为含0．1％三乙胺的10mmol／L十二烷基硫酸钠溶液（用磷酸调pH3．4）-乙腈（55：45），流速为1．0ml／min，检测波长为205nm。结果：依托红霉素在0．55～2．75mg／ml浓度范围内，峰面积与其浓度呈良好的线性关系，r=0．9992（n=5），平均回收率为99.3％，RSD为1．26％（n=6）。结论：本法简便、准确、灵敏度高、重复性好，可作为复方依托红霉素洗剂中依托红霉素含量的测定方法。     

浓缩鱼肝油滴剂加红霉素治疗儿童口腔溃疡的临床观察

目的 观察浓缩鱼肝油滴剂加红霉素治疗儿童口腔溃疡的疗效。方法 将162例口腔溃疡患儿，随机分为2组。实验组局部给予浓缩鱼肝油滴剂加红霉素粉针剂混合。涂搽溃疡面，对照组局部撒敷冰硼散，观察2组患儿口腔渍疡愈合时间。结果 实验组总有效率高于对照组（P〈0．01）。结论 浓缩鱼肝油滴剂加红霉素可促进溃疡愈合。     

注射用阿奇霉素治疗呼吸道感染的临床疗效

目的：评价注射用阿奇霉素治疗呼吸道感染的疗效与安全性。方法：利用随机对照研究方法，将71例轻中度呼吸道感染病人随机分为两组。试验组用阿奇霉素治疗，首次500mg，每天1次，以后用250mg，每天1次静脉滴注，疗程共5d。对照组用红霉素治疗，每天1000－1250mg，每天1次，静脉滴注，疗程7－10d。结果：两药的临床疗效和细菌学疗效相似，但试验药不良反应发生率低，试验组不良反应发生率为8．57％，对照组27．78％。结论：注射用阿奇霉素治疗急性呼吸道感染有效且不良反应更低。     

Effect of erythromycin and itraconazole on the pharmacokinetics of intravenous lignocaine

Objective: We have studied the possible interaction of erythromycin and itraconazole, both inhibitors of cytochrome P450 3A4 isoenzyme (CYP3A4), with intravenous lignocaine in nine healthy volunteers using a randomized cross-over study design. Methods: The subjects were given oral placebo, erythromycin (500 mg three times a day) or itraconazole (200 mg once a day) for 4 days. Intravenous lignocaine 1.5 mg · kg⁻¹ was given with an infusion for 60 min on the fourth day of pretreatment with placebo, erythromycin or itraconazole. Timed plasma samples were collected until 11 h. The concentrations of lignocaine and its metabolite monoethylglycinexylidide (MEGX) were measured by gas chromatography. Results: The area under the lignocaine concentration-time curve was similar during all three phases but erythromycin significantly increased the elimination half-life of lignocaine from 2.5 to 2.9 (0.7) h compared with placebo. Following itraconazole administration, t_1/2 was 2.6 h. The values for plasma clearance and volume of distribution at steady state were similar during all the phases. Compared with placebo and itraconazole, erythromycin significantly increased MEGX peak concentrations by approximately 40% and AUC_(0–11 h) by 45–60%. Conclusion: The plasma decay of lignocaine administered intravenously is virtually unaffected by the concomitant administration of erythromycin and itraconazole. However, erythromycin increases the concentrations of MEGX, which indicates that erythromycin either increases the relative amount of lignocaine metabolized via N-de-ethylation or decreases the further metabolism of MEGX. Further studies are necessary to elucidate the clinical significance of the erythromycin-induced elevated concentrations of MEGX during prolonged intravenous infusions of lignocaine. Received: 8 January 1998 / Accepted in revised form: 8 June 1998     

Studies on the intravenous pharmacokinetics in rabbit and in vitro protein binding of two new salts of erythromycin: erythromycin maltobionate and erythromycin fumarate.

Pharmacokinetics in rabbits following intravenous administration and in vitro protein binding were studied for two new salts of erythromycin (erythromycin maltobionate and erythromycin fumarate). Serum erythromycin levels following intravenous injection were described by two compartment model kinetics, and values for the distribution volume of the central compartment, the peripheral compartment and overall distribution volume were calculated. The elimination half-lives of erythromycins in serum were 83 min, 168 min, and 103 min for erythromycin maltobionate, erythromycin fumarate, and erythromycin lactobionate (reference standard), respectively. The erythromycin salts were highly (c. 90 per cent) protein bound, but the binding was found to be reversible. Differences in the pharmacokinetic parameters after administration of equivalent doses of the salts, indicate possible variation in efficacies of different salts.     

Azithromycin的体内抗菌作用研究

口服ａｚｉｔｈｒｏｍｙｃｉｎ对金葡球菌，肺炎球菌，化脓性链球菌各２株感染小鼠的ＦＤ５０值分别为５１．４０和５８．７４ｍｇ／ｋｇ，２０．４０和２８．７４ｍｇ／ｋｇ，２０．９０和２１．７４ｍｇ／ｋｇ比对照药红霉素的ＥＤ５０（１０１．４２和１０６．８４ｍｇ／ｋｇ，１０４．１２和１６５．７９ｍｇ／ｋｇ，４３．７１和４３．４８ｍｇ／ｋｇ）低，两药ＥＤ５０值经学处理有显著性差异（Ｐ〈０．０１）。     

红霉素链霉菌遗传控制的研究 2.红霉素链霉菌耐前体耐红霉素高产菌株的筛选

利用长波紫外线和8-甲氧基补骨脂素光敏化物质诱变处理红霉素链霉菌14-74,在含有红霉素或和前体的培养基中,筛选得到了红霉素高产变株。在含有红霉素2万μg/ml 的种子培养基中,筛得活性提高6.2%的耐性变株;在含有6%正丙醇的种子培养基中,得到活性提高12.4%的耐性变株。将耐红霉素3万μg/ml 的变株进一步用长波紫外线诱变处理,在含有5%正丙醇的种子培养基中进行筛选,得到耐红霉素和正丙醇,活性提高19.1%的变株。     

Combination vinorelbine and capecitabine for metastatic breast cancer using a non-body surface area dosing scheme

Purpose: This study sought to determine the maximum tolerated dose of flat-dosed vinorelbine in combination with capecitabine in patients with metastatic breast cancer. At the time of study initiation, it was anticipated that vinorelbine would be developed as an oral capsule. A flat dosing scheme of both drugs was used to facilitate development of the oral regimen, and because neither drug’s clearance is associated with body surface area (BSA), pharmacokinetic and pharmacogenetic endpoints were explored. Experimental Design: Capecitabine was administered orally at 3,000 mg/day on days 1–14. The starting dose of vinorelbine was 20 mg intravenously on days 1 and 8 of a 21-day cycle. The vinorelbine dose was escalated until dose limiting toxicity (DLT). Vinorelbine pharmacokinetics were measured after the first dose. Patients underwent genotype analysis for polymorphisms in the CYP3A5 gene, and the erythromycin breath test (ERMBT), a phenotypic test of CYP3A enzyme activity. Results: Twenty five eligible patients were enrolled. Hematologic DLT was seen at the 50 and 45 mg vinorelbine doses; thus the recommended dose is 40 mg on days 1 and 8. Response rate was 30%, and disease stabilization rate was 64% (all dose levels included). Vinorelbine clearance was not associated with ERMBT, BSA, or age. CYP3A5 genotype in this small sample did not have an obvious relationship to clearance or toxicity. Conclusions: A non-BSA based dosing scheme of capecitabine and vinorelbine is safe and efficacious. BSA did not affect vinorelbine clearance. We recommend future studies with capecitabine and/or vinorelbine to compare the safety and efficacy of flat dosed versus BSA-dosed treatment.     

红霉素对钾离子通道HERG高表达癌细胞的增殖抑制及其与化疗药物的协同作用

目的研究红霉素对钾离子通道HERG高表达癌细胞的增殖抑制及其与化疗药物的协同作用。方法采用Western印迹、四甲基偶氮唑蓝（MTT）法、流式细胞术、细胞黏附实验以及明胶酶谱法观察红霉素对肿瘤细胞的作用。结果HERG钾通道在人结肠癌HT-29细胞和小鼠结肠癌C26细胞中均有表达,和HERG钾通道高表达对照神经母细胞瘤SH-SY5Y相比,在HT-29细胞中表达量较高。红霉素对HT-29细胞和C26细胞的增殖具有不同程度的抑制作用,呈浓度依赖性。红霉素能将HT-29细胞阻滞于G2／M期,并引起明显的Sub G1峰。红霉素对HT-29细胞黏附于Ⅰ型胶原具有明显的抑制作用,存在明显的剂量-效应关系。红霉素能抑制肿瘤细胞释放明胶酶MMP-2。红霉素与长春新碱协同抑制小鼠C26细胞的增殖。长春新碱单用以及长春新碱与红霉素（50μmol／L）联用的IC50分别为62．65nmol／L和4．68nmol／L。红霉素与紫杉醇、羟基喜树碱联用亦显示协同作用。结论红霉素在能抑制钾离子通道HERG高表达癌细胞HT-29的增殖,并能诱导肿瘤细胞凋亡。红霉素与长春新碱等化疗药物显示协同作用。