陈桂林，翁春梅， 刘广军，杜贯涛(常州市第二人民医院药学部，江苏 常州　213003)



氨溴索对大鼠肺组织中氟康唑药物浓度的影响Δ

陈桂林*，翁春梅#， 刘广军，杜贯涛(常州市第二人民医院药学部，江苏 常州213003)

DOI10.14009/j.issn.1672-2124.2016.03.032

摘要目的：建立测定大鼠肺组织中氟康唑的高效液相色谱-紫外吸收检测(HPLC-UV)法，探讨氨溴索对大鼠肺组织中氟康唑药物浓度的影响。方法：将实验大鼠按随机数字表法分为A、B组，每组各10只，A组大鼠首日经尾静脉给予72 mg/kg注射用氟康唑，以后给予1日36 mg/kg；B组大鼠先经胃灌注给予6 mg/kg氨溴索，1日2次，上午给予氨溴索30 min后给予注射用氟康唑。连续给药2 d后，第3日给予氟康唑后2 h对大鼠颈静脉取血后解剖，取肺组织备用。采用HPLC-UV法同时测定最后一次使用氟康唑后2 h大鼠的肺组织浓度。结果：氟康唑线性范围均为2.5～80 μg/ml之间，回归方程为X=0.052C-0.027 6，相关系数r=0.999 9。A组大鼠肺组织氟康唑的浓度(28.1±19.6)μg/ml，B组为(26.6±17.7)μg/ml，2组的差异无统计学意义(P<0.05)。结论：氨溴索对肺组织中的氟康唑药物浓度无显著影响，但尚需结合临床实际行进一步的研究。

关键词氟康唑； 氨溴索； 药物浓度； 高效液相色谱一紫外吸收检测法

Effects of Ambroxol on Concentration of Fluconazole in Rat Lung TissueΔ

CHEN Guilin, WENG Chunmei, LIU Guangjun, DU Guantao (Dept.of Pharmacy, Changzhou the Second People’s Hospital, Jiangsu Changzhou 213003, China)

ABSTRACTOBJECTIVE：To establish a HPLC-UC method of fluconazole and explore effects of ambroxol on concentration of fluconazole in rat lung tissue. METHODS: Rats were divided into group A and group B via the random number table, with 10 cases in each. And group A were treated with 72 mg/kg fluconazole injection by caudal vein in the first day, followed by 36 mg/kg for a day during the latter treatment. Group B received 6 mg/kg ambroxol by abomasum infusion, twice a day, and after the administration of ambroxol for 30 min in the morning, fluconazole injection was given. After administration of 2 d, 2 h after administration of fluconazole in the 3rdday, the blood was drawn from jugular vein of rats and then anatomy was conducted, lung tissue of rats were taken. HPLC-UV method was adopted to determine the concentration of rat lung tissue 2 hours after injecting fluconazole in the last administration. RESULTS: The calibration curve was linear with the logarithm of concentration range of 2.5～80 μg/ml of fluconazole ,he linear equation wasX=0.052C-0.027 6, the correlation coefficientr=0.999 9.The concentration of fluconazole in the lung tissue of group A was(28.1±19.6)μg/ml, and in group B was(26.6±17.7)μg/ml, the difference was not statistically significant(P<0.05). CONCLUSIONS: Ambroxol has no significant effect on concentration of fluconazole in the lung tissue, yet it still needs the further research combined with the clinical practice.

KEYWORDSFluconazole; Ambroxol; Drug concentration; HPLC-UC method

近年来，由于大剂量广谱抗菌药物的长期应用及造血干细胞移植、实体器官移植的广泛开展，侵袭性肺部真菌感染的发病率明显上升。目前，已知侵袭性肺部真菌感染最常见的致病菌为念珠菌，初始治疗时首选氟康唑[1]。然而，氟康唑的广泛使用导致了白念珠菌耐药性的逐年增加[2-3]。有报道称，氨溴索能明显增加氨苄西林、阿莫西林、红霉素等多种抗菌药物在肺组织中的药物浓度[4]，临床常见氟康唑与氨溴索联合使用，但至今无氨溴索对氟康唑在肺组织中药物浓度影响的报道。……