Selective spectrophotometric determination of phenolic β-lactam antibiotics

Two simple and selective spectrophotometric methods were developed for the quantitative determination of cefoperazone sodium, cefadroxil monohydrate, cefprozil anhydrous and amoxicillin trihydrate in pure forms as well as in their pharmaceutical formulations. The methods are based on the selective oxidation of these drugs with either Ce (IV) or Fe (III) in acid medium to give an intense yellow coloured product (λ_max=397 nm). The reaction conditions were studied and optimized. Beer's plots were obeyed in a general concentration range of 5–30 μg ml⁻¹ with correlation coefficients not less than 0.9979 for the four drugs with the two reagents. The methods are successfully applied to the analysis of pharmaceutical formulations containing amoxicillin, either alone or in combination with potassium clavulanate, flucloxacillin or dicloxacillin. They were also applied to the analysis of the other three studied drugs in vials, capsules, tablets and suspensions with good recovery; percent ranged from 99.7 (±0.46) to 100.32 (±1.05) in the Ce (IV) method and 99.6 (±0.50) to 100.3 (±1.32) in the Fe (III) method. Interferences from other antibiotics and additives products were investigated.     

国产头孢哌酮/舒巴坦钠治疗老年下呼吸道细菌性感染的临床疗效评价

目的　评价国产头孢哌酮 /舒巴坦钠治疗老年下呼吸道细菌性感染的临床疗效。方法　中、重度感染患者 6 0例随机分为观察组和对照组 ,各 30例。观察组应用国产头孢哌酮 /舒巴坦钠治疗 ,对照组使用头孢哌酮钠治疗。结果观察组和对照组临床有效率分别为 93.3%、90 .0 % ;细菌转阴率 92 .6 %、88.5 % ;产酶菌转阴率 89.5 %、82 .4 % ;细菌清除率 85 .2 %、80 .8% ;细菌敏感率 94 .3%、90 .6 % ;不良反应发生率 6 .6 7%、3.33% (P >0 .0 5 )。两组效价比分别为 (0 .39± 0 .2 9)与 (0 .19± 0 .11) (P <0 .0 5 )。结论　国产头孢哌酮 /舒巴坦钠效价比较高 ,临床试验结果满意 ,适于治疗中、重度老年下呼吸道细菌性感染 ,并有利于降低整体医疗费用成本。     

Comparison of safety between high and low doses of sulbactam/ampicillin: A retrospective observational study in Japanese patients with pneumonia

Although 12 g/day sulbactam/ampicillin (SBT/ABPC) is approved in Japan, differences in the frequency of adverse effects induced by conventional (≤6 g/day) and high (≥9 g/day) doses remain unclear. We performed a retrospective observational study on SBT/ABPC-treated hospitalized adult patients with pneumonia from October 2015 to January 2018 to compare the safety between high and low doses. Patients were divided into high-dose (≥9 g/day, n = 200) and low-dose (≤6 g/day, n = 246) groups. We used logistic regression to determine propensity scores for the high-dose and low-dose groups and compared the incidence of adverse effects after propensity score adjustment (n = 200 in each group). Following propensity score adjustment, the frequency of elevated alanine aminotransferase (ALT) level was still significantly higher in the high-dose group than in the low-dose group (21% versus 11%, p = 0.006). In contrast, the frequencies of elevated alkaline phosphatase, aspartate aminotransferase, and serum creatinine levels and decreased white blood cell and platelet counts, and incidence of anemia, were not. Changes in blood urea nitrogen levels, erythrocyte count, and hematocrit were not significantly different between the two dose groups. There were two cases of rash reported to the Pharmaceuticals and Medical Devices Agency as an adverse effect in the high-dose group. Thirty-day mortality rates were not significantly different after propensity score adjustment. Our analysis suggests that an increase in the ALT grade was more frequent in patients treated with a daily dose of SBT/ABPC of ≥9 g.     

高效液相色谱法测定家兔离体血液中头孢哌酮衰除速度的实验研究

目的比较家兔体内与体外头孢哌酮衰除速度的差异,了解离体血液中头孢哌酮对受血者的影响。方法健康家兔20只,体重(3±0.3)kg,随机分为实验组(离体组)和(在体组)各10只,2组均从兔耳缘静脉注射头孢哌酮150mg/kg,实验组于给药45min后从耳缘静脉取血(8—10)ml/只,置于(4±2)℃冰箱保存,用高效液相色谱法测定0、6、12、24、48、72、120和168h血药浓度;对照组分别于给药后1、2、3、4、5h从耳缘静脉取血1ml/只(次),用高效液相色谱法测定血药浓度;分别计算兔离体和在体血液中头孢哌酮的半衰期。结果实验组血液中头孢哌酮的消除半衰期为(146.08±9.56)h,对照组则为(1.55±0.048)h。离体血液中头孢哌酮的半衰期较在体血液中头孢哌酮的半衰期显著延长(P<0.01)。结论离体血液中头孢哌酮代谢较慢,不能在血液储存期内衰除到安全浓度水平以下,输血时可能引起受血者产生药物不良反应。     

阿莫西林钠/舒巴坦钠与氨苄西林钠/舒巴坦钠随机对照治疗急性细菌性感染临床研究

目的：本研究对阿莫西林钠／舒巴坦钠与氨苄西林钠／舒巴坦随机单盲对照治疗中、重度急性细菌性感染，评价阿莫西林钠／舒巴坦钠的有效性与安全性。方法：采用区组随机单盲对照试验设计，完成试验药20例及对照药19例感染患者的临床试验。结果：两组病例的一般项目基本相似，阿莫西林钠／舒巴坦钠和氨苄西林／舒巴坦钠治疗各种细菌感染的临床有效率分别为85．00％与89．47％，细菌学有效率为分别为80．00％和86．67％，细菌清除率为93．33％与100％，临床分离细菌的产酶率均为66．67％。两组病例的不良反应发生率分别为10．00％和10．53％，不良反应轻微，不需特殊处理，停药后可自行恢复正常。结论：阿莫西林钠／舒巴坦钠是一种安全有效治疗细菌感染的药物，对β－内酰胺酶产生菌也同样有较好疗效，可用于治疗多种细菌引起的各种感染。     

UPLC测定注射用头孢哌酮钠舒巴坦钠

目的:建立超高效液相色谱检测注射用头孢哌酮钠舒巴坦钠含量及有关物质的方法。方法:采用ACQUITY UPLC HSSC18色谱柱,以0.1%磷酸水溶液和乙腈为流动相进行梯度洗脱,流速0.45 mL.min-1,检测波长为220 nm,柱温为30℃。结果:头孢哌酮与舒巴坦在20～150μg.mL-1范围内r≥0.9998,各杂质均呈良好的线性关系;头孢哌酮平均回收率为99.9%,RSD为0.40%;舒巴坦平均回收率为99.5%,RSD为0.36%;重复性、专属性、供试品溶液稳定性良好,各组分之间互相无干扰。结论:该方法专属性强、灵敏度高、准确性好,可以作为注射用头孢哌酮钠舒巴坦钠含量测定及有关物质检查的有效方法。     

头孢哌酮/舒巴坦钠与亚胺培南/西司他丁钠治疗肺部感染最小成本分析

目的:评价头孢哌酮/舒巴坦钠(舒普深,CPZ-SB)与亚胺培南/西司他丁钠(泰能I,MP)治疗肺部感染的经济学效果。方法:运用最小成本分析法,对分别以2种治疗方案治疗肺部感染的临床疗效及成本进行评价。结果:CPZ-SB组和IMP组总有效率分别为92.68%、78.05%,细菌清除率分别为57.14%、50%,均无统计学意义(P>0.05)。CPZ-SB组和IMP组的治疗成本分别为3 184.55、1 732.65元,成本-效果比分别为34.362、2.20。结论:从药物经济学角度看I,MP组方案较佳。     

头孢哌酮钠舒巴坦钠治疗下呼吸道感染的临床观察

目的观察头孢哌酮钠舒巴坦钠治疗下呼吸道感染的临床疗效和安全性。方法将101例下呼吸道感染患者随机分为头孢哌酮钠舒巴坦钠2.0g/次,次/12h治疗组52例（A组）和头孢他啶2.0g/次,次/12h对照组49例（B组）,疗程均为7-14 d。比较两组临床疗效、细菌学改变及不良反应情况。结果 A、B组临床有效率分别为90.38%、85.71%,细菌清除率分别为94.23%、89.8%,二者比较差异无统计学意义（P〉0.05）。结论头孢哌酮钠舒巴坦钠治疗下呼吸道感染安全、有效。     

正负离子切换液相色谱-串联质谱法同时测定人血浆中头孢他啶和他唑巴坦

目的:建立灵敏、专属的液相色谱-串联质谱法同时测定人血浆中头孢他啶和他唑巴坦,并用于临床药代动力学研究。方法:血浆样品经乙腈沉淀蛋白后,以乙腈-5 mmol.L-1醋酸铵-甲酸(20∶80∶0.16,v/v/v)为流动相,使用VenusilASB-C18柱(150 mm×4.6 mm,5μm)分离。采用电喷雾电离源,多反应监测模式(MRM),以正负离子切换同时测定头孢他啶和他唑巴坦,切换时间在进样后3.8 min。头孢他啶采用正离子检测,用于定量的离子反应分别为m/z 547→468(头孢他啶),m/z 364→208(内标头孢羟氨苄),头孢他啶和内标头孢羟氨苄的保留时间分别为3.0 min和2.8 min;他唑巴坦采用负离子检测,用于定量的离子反应分别为m/z 299→138(他唑巴坦),m/z 232→140(内标舒巴坦),他唑巴坦和内标舒巴坦的保留时间分别为4.4 min和4.9 min。结果:头孢他啶和他唑巴坦的线性范围分别为0.250～250μg.mL-1和0.0250～25.0μg.mL-1,日内、日间精密度(RSD)均小于10.8%,准确度(RE)在-7.6%～2.1%之间。本法被成功应用于健康受试者静脉滴注不同剂量头孢他啶/他唑巴坦钠(6∶1)注射液(头孢他啶/他唑巴坦含量分别为1 g/0.167 g,2 g/0.333 g,4 g/0.667 g)的药动学研究。结论:该方法专属性强,灵敏度高,操作简便,适用于注射用头孢他啶/他唑巴坦临床药代动力学研究。     

注射用头孢哌酮钠/舒巴坦钠致过敏性休克死亡1例

目的引起临床医师及药师的重视,促进临床安全用药。方法报告1例注射用头孢哌酮钠/舒巴坦钠严重不良反应,分析基本情况并对此提出建议。结果注射用头孢哌酮钠舒巴坦钠严重不良反应在多重因素影响下,可导致患者死亡。结论应继续加强该药物的不良反应监测。