Garenoxacin Prophylaxis for Febrile Neutropenia after Chemotherapy in Hematological Malignancies

Background: Febrile neutropenia is one of the most serious adverse events in patients with hematological malignancies and chemotherapy. The routine use of fluoroquinolone prophylaxis in patients with hematological malignancies is controversial. Therefore, we prospectively evaluated the efficacy and safety of prophylactic use of garenoxacin for febrile neutropenia. Patients and Methods: Consecutive adult patients with hematological malignancies who were at risk for chemotherapy-induced neutropenia lasting more than seven days were eligible for present study. They received oral garenoxacin (400 mg daily) from the neutrophil count decreased to less than 1000/μl and continued until the neutropenia had resolved. The primary endpoint was incidence of febrile neutropenia, and the secondary endpoints were the type and incidence of adverse events. Results: We enrolled 46 consecutive patients (median age, 59 years). The underlying diseases comprised acute myeloid leukemia (n = 17), acute lymphoblastic leukemia (n = 3), malignant lymphoma (n = 23), and multiple myeloma (n = 3). There were 23 febrile neutropenia episodes and 2 episodes of bacteremia. There were no grade 3 or 4 adverse events;however serum creatinine levels were significantly elevated after garenoxacin administration. The overall prophylactic efficacy of garenoxacin was 50%, and there were no infection-related deaths. Conclusions: Prophylactic use of garenoxacin is effective and safe in patients with hematological malignancies. (Clinical trial registration number: UMIN000004979).

加雷沙星的吸附伏安法测定

在0.3mol.L-1KH2PO4-Na2HPO4(pH6.40)底液中,加雷沙星(Garenoxacin,简称GRX)在汞电极上有一线性扫描还原峰,峰电位EP=-1.12V(vsAg/AgCl),该峰具有明显的吸附性;吸附粒子为GRX中性分子,测得GRX在汞电极上的饱和吸附量Гs=3.92×10-11mol.cm-2,每个GRX分子所占电极面积为1.94nm2,GRX在汞电极上的吸附符合Langmuir吸附等温式;测得吸附系数β=1.14×106,25℃时的吸附自由能ΔGθ=-29.62kJ.mol-1,电极反应电子数n=2,不可逆体系动力学参量αna=1.04,表面电极反应速率常量ks=0.25s-1;建立了吸附溶出伏安法测定GRX的最佳条件,方法的检出限为2.0×10-8mol.L-1。

Antibiotic Treatment for Chronic Rhinosinusitis after Endoscopic Surgery: How Long Should Macrolide Antibiotics Be Given?

Background: The purpose of this study was to determine an appropriate period for macrolide antibiotic therapy, and to investigate whether this period could be shorter, for patients with chronicrhino sinusitis (CRS) after functional endoscopic sinus surgery (FESS). Methods: A retrospective analysis of 41 patients undergoing FESS for CRS was performed. All patients underwent pre-operative computed tomography (CT). Patients with fungal sinusitis, allergic fungal sinusitis, and eosinophilic sinusitis were excluded. After FESS, normalized sinus mucosa was confirmed by CT and endoscopy in all patients. Postoperative antibiotic therapy consisted of first-line and second-line regimens. Garenoxacin (GRNX), or clarithromycin (CAM, 400 mg/day) was used as the first-line regimens and low-dose macrolide therapy (CAM, 200 mg/day) was used as the second-line regimen and was prescribed at outpatient visits based on our clinical criteria. Results: Second-line antibiotic therapy (low-dose CAM) was not necessary in 12 of 41 (29%) patients, while it was prescribed in 29 of 41 (71%). The mean duration of low-dose CAM therapy after FESS was 36 days (range 7 to 122 days;median, 25 days). Patients who received second-line therapy (n = 29) were divided into two groups based on the choice of first-line therapy, a GRNX group (n = 13) and a non-GRNX group (n = 16). Those in the non-GRNX had longer periods of postoperative CAM therapy than those in the GRNX group. Conclusion: GRNX was associated with a shorter duration of low-dose macrolide therapy after FESS, and 29% of patients did not need any low-dose macrolide therapy postoperatively. Therefore, macrolide antibiotics should not be routinely prescribed after FESS.

基于人群研究药代动力学/药效学和蒙特卡罗模拟加雷沙星最佳剂量

目的:探讨基于人群研究药代动力学/药效学和蒙特卡罗模拟加雷沙星的最佳剂量。方法:患者给予加雷沙星400 mg,1次/d,共10 d,评价临床疗效。结果:92.4%(61/66)达到f AUC0-24/MIC比值>30 h的目标值,临床有效率91.8%(56/61)。结论:对于呼吸道感染患者,加雷沙星的理想剂量以每天1次400 mg为宜。

中国健康受试者单次空腹口服加诺沙星片药动学研究

目的研究加诺沙星片200 mg、400 mg和600 mg在中国健康成年受试者中的药动学及安全性。方法采用三剂量、单剂给药、单周期、开放、平行试验设计,观察24名受试者分别单次空腹口服加诺沙星片200 mg、400 mg和600 mg后药动学特征。通过体格检查、生命体征、12-导联心电图及其他临床和实验室检查评价不良事件,分析加诺沙星安全性。以超高效液相串联质谱法检测人血浆及尿液样本中加诺沙星浓度,进行药动学参数计算并分析线性药动学特征。结果单次空腹口服加诺沙星片200 mg、400 mg和600 mg后,峰浓度分别为4.64 mg/L、10.59 mg/L和14.44 mg/L,药时曲线下面积(AUC_(0-∞))分别为52.9 mg·h/L、117.0 mg·h/L和169.6 mg·h/L,平均末端消除半衰期约为10 h,48 h内平均累积尿排出占给药量41.9%~54.2%。在200~600 mg剂量范围内,加诺沙星体内峰浓度(C_(max))和AUC_(0-∞)对给药剂量回归斜率分别为1.05(95%CI:0.82~1.28)和1.06(95%CI:0.93~1.20)。发生1例次轻度不良事件,无重要不良事件发生。结论中国健康受试者空腹单次口服加诺沙星片200 mg、400 mg和600 mg后仅发生1例次不良事件,提示安全性和耐受性良好。加诺沙星C_(max)和AUC_(0-∞)对剂量回归斜率95%CI均包含1,提示药物暴露量与剂量呈比例关系增加。

氟喹诺酮药物格林沙星抗体制备及其icELISA方法建立

目的：制备格林沙星多克隆抗体并建立间接竞争酶联免疫吸附分析方法（icELISA）。方法：采用碳二亚胺法将格林沙星偶联于牛血清白蛋白（BSA）作为免疫原,免疫新西兰大白兔获多克隆抗体;采用活泼脂法分别将格林沙星、克林沙星、加替沙星、培氟沙星和沙拉沙星偶联于卵清白蛋白（OVA）,制备5种包被抗原并做性能比较;建立icELISA方法并对其灵敏度和特异性进行评价。结果：成功制备了免疫原和包被抗原及抗体,抗体效价最高达64 000倍。以克林沙星-OVA作异源包被,建立的icELISA方法灵敏度最高,半抑制药物浓度（IC50）为9.14 ng/mL,检测限（IC10）为0.9 ng/mL,检测范围（IC20~IC80）为2.3~36.4 ng/mL,与其他喹诺酮类药物无明显交叉反应。结论：首次制备出格林沙星抗体并建立间接竞争酶联免疫吸附检测方法,该法灵敏度高、特异性强,为分析生物样品中格林沙星含量的测定提供了1种新的方法。

HPLC测定甲磺酸加雷沙星异构体

目的 建立甲磺酸加雷沙星异构体的HPLC检测方法。方法 Chiralpak AD-H色谱柱（250 mm×4.6 mm,5μm）,柱温：35℃,检测波长：278 nm,流速：1.0 m L·min-1,流动相：正己烷-异丙醇-甲醇-甲磺酸（70∶29∶1∶0.1）。结果 甲雷沙星及其异构体在0.005~0.151μg·m L-1内具有良好的线性（r〉0.999）,定量限浓度为5 ng·m L-1（相当于0.03%）,最低检测限为2.5 ng·m L-1（相当于0.015%）。结论 该方法简便、准确,具有良好的重现性和专属性。

加雷沙星的合成

目的合成加雷沙星。方法1(R)-甲基-5-溴-1H-异吲哚啉经N-烷基化、硼酸化、缩合、去保护反应制得加雷沙星。结果通过优化条件合成了加雷沙星,总收率51.0%,目标化合物结构经红外、质谱、核磁共振谱、元素分析确证。结论本工艺步骤少,原材料价廉易得,适合工业化生产。