注射用头孢呋辛钠他唑巴坦钠Ⅰ期临床耐受性试验  

Phase Ⅰ clinical trial on safety and tolerability of cefuroxime sodium and tazobactam sodium for injection

作　　者：勾忠平[1] 冯萍[1] 郑莉[1] 徐楠[1] 

机构地区：[1]四川大学华西医院国家药物临床试验机构,成都610041

出　　处：《中国新药杂志》2016年第1期87-92,共6页Chinese Journal of New Drugs

摘　　要：目的：观察中国健康志愿者静脉滴注注射用头孢呋辛钠他唑巴坦钠后的安全性和耐受性。方法：单次给药40例受试者分为7个剂量组,分别给予注射用头孢呋辛钠他唑巴坦钠0.75,1.5,3.0,4.5,6.0,7.5和9.0 g;多次给药12例受试者分为2个剂量组,分别给予注射用头孢呋辛钠他唑巴坦钠2.25和3.0 g,tid,连续给药7 d。观察用药后受试者的生命体征、临床症状和体征、实验室检查、心电图检查以及不良事件。结果：52例受试者完成单次、多次给药试验。52例受试者中有9例发生14例次不良事件,总不良反应发生率为15.38%（8/52）,其中白细胞减少为7.69%（4/52）、中性粒细胞减少为5.77%（3/52）、腹痛为3.85%（2/52）、其他为恶心、稀便、血红蛋白减少、谷丙转氨酶升高均为1.92%（1/52）,均为轻度。上述不良反应与报道的已上市头孢呋辛或他唑巴坦的不良反应情况相似。单次、多次给药试验中均未发生严重不良事件。结论：注射用头孢呋辛钠他唑巴坦钠单次给药0.75~9.0 g或多次给药每次3.0 g（tid,连续7 d）安全且耐受性好,单次给药的最大耐受剂量为9.0 g。推荐Ⅱ期临床试验的给药剂量为每次1.5~3.0 g,tid。Objective： To assess the safety and tolerability of cefuroxime sodium and tazobactam for injection in Chinese healthy volunteers. Methods： Forty healthy subjects were enrolled in the single-dose trial,and 12 healthy subjects were enrolled in the multiple-dose trial. Subjects in cohort 1 to 7 received intravenous infusion of single dose of 0. 75,1. 5,3. 0,4. 5,6. 0,7. 5 and 9. 0 g cefuroxime sodium and tazobactam sodium for injection.Subjects in cohort 8 and 9 received intravenous infusion of 2. 25 g and 3. 0 g three times daily for consecutive 7days. The safety and tolerability were evaluated based on clinical symptoms,vital signs,physical examinations,ECG,laboratory tests and adverse events. Results： Totally,52 healthy volunteers completed the single-and multiple-dose trials. Fourteen adverse events were observed in 9 subjects among 52 subjects,and the adverse drug reactions（ ADRs） rate was 15. 38%（ 8 /52）. The ADRs,including leucopenia（ 7. 69%）,neutropenia（ 5. 77%）,abdominal pain（ 3. 85%）,loose stool（ 1. 92%）,nausea（ 1. 92%）,hemoglobin decrease（ 1. 92%） and alanine aminotransferase（ ALT） elevation（ 1. 92%）,were all mild,which were similar to those reported for cefuroxim and tazobactam. No serious adverse events occurred in either of single-and multiple-dose groups. Conclusion： Cefuroxime sodium and tazobactam sodium for injection is safe and well tolerated in Chinese healthy subjects after administration of single-dose of 0. 75 ~ 9. 0 g and multiple-dose of 3. 0 g three times daily for 7 days. The maximum tolerated dose is 9. 0 g for single-dose administration,and the recommended dose regimen is 1. 5 ~ 3. 0 g three timesdaily for phase Ⅱ study.

关 键 词：注射用头孢呋辛钠他唑巴坦钠 单次给药 多次给药 健康受试者 Ⅰ期临床试验 耐受性 安全性 

分 类 号：R978.1[医药卫生—药品]