目的 探索中药制剂清毒胶囊对高效抗逆转录病毒治疗药物药动学的影响。方法 36只SD大鼠随机分为3组,每组12只,高效抗逆转录病毒治疗组给予单纯高效抗逆转录病毒治疗一线方案齐多夫定(zidovudine,AZT)+拉米夫定(2′, 3′-dideoxy-3′-thiacytidine,3TC)+依非韦伦(efavirenz,EFV),高效抗逆转录病毒治疗+清毒胶囊组同时给予高效抗逆转录病毒治疗和清毒胶囊,高效抗逆转录病毒治疗+清毒胶囊(间隔2 h)组给予高效抗逆转录病毒治疗,间隔2 h再给予清毒胶囊,灌胃给药,在0、0.5、1、2、3、4、6、8、10、12 h眼眶采血,高效液相-液质联用法(HPLC-MS/MS)检测齐多夫定、拉米夫定、依非韦伦的血药浓度,比较各组药动学参数。结果 齐多夫定的t1/2的组间差异有统计学意义(P<0.05),高效抗逆转录病毒治疗+清毒胶囊(间隔2 h)组的t1/2较小;齐多夫定的AUC0-12、CL、ρmax和tmax以及拉米夫定、依非韦伦各项药动学参数的组间差异均无统计学意义。结论 清毒胶囊对齐多夫定+拉米夫定+依非韦伦治疗方案的药动学参数无明显影响,但需注意个体差异。
Abstract
OBJECTIVE To assess the influence of Qingdu (QD) capsule on the pharmacokinetic of HAART. METHODS The 36 SD rats were divided into 3 groups. Rats in Group HAART were given, using an intragastric gavage needle, highly active antiretroviral therapy (HAART) containing zidovudine (AZT), 2′,3′-dideoxy-3′-thiacytidine (3TC) and efavirenz (EFV). Group HAART+QD were given HAART and QD capsule simultaneously. Group HAART+QD (2 h interval) were given HAART and then given QD capsule 2 h later. Blood samples were collected at 0, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 h. AZT, 3TC, and EFV concentrations were tested with high performapce liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Pharmacokinetic parameters were compared among different groups. RESULTS The t1/2 of AZT were statistically different among the three groups (P<0.05), Group HAART+QD (2 h interval) had the lease t1/2 of AZT than the other two groups. There were no statistical differences among groups for the AUC0-12,tmax, ρmax and CL of AZT, and all five parameters of 3TC and EFV. CONCLUSION QU doesn′t show influence on pharmacokinetic parameters of AZT+3TC+EFV regimen, but intention should be paid to individual differences.
关键词
药动学 /
中药 /
清毒胶囊 /
高效抗逆转录病毒治疗 /
血药浓度
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Key words
pharmacokinetics /
Chinese medicine /
Qingdu capsule /
highly active antiretroviral therapy (HAART) /
blood drug concentration
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中图分类号:
R969.1
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参考文献
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脚注
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基金
国家自然科学基金资助项目(81360258);广西自然科学基金资助项目(2014GXNSFAA118175)
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