葛根芩连汤对吡格列酮在大鼠体内药动学行为的影响
|
摘要
目的考察葛根芩连汤对吡格列酮在大鼠体内药动学行为的影响。方法实验大鼠随机分成吡格列酮组和葛根芩连汤+吡格列酮组,每组6只,分别给予单次灌胃给药(生理盐水或14 g/kg葛根芩连汤,30 min后3 mg/kg吡格列酮)和多次灌胃给药(生理盐水或14 g/kg葛根芩连汤,每天1次,连续7 d,第8天生理盐水或14 g/kg葛根芩连汤,30 min后3 mg/kg吡格列酮)。LC-MS/MS法测定吡格列酮血药浓度,计算药动学参数。结果多次给药后,葛根芩连汤+吡格列酮组AUC、MRT_(0～)_t、C_(max)、T_(max)显著高于吡格列酮组(P<0.05,P<0.01),CL_z/F显著降低(P<0.01);较单次给药MRT_(0～)_t、t_(1/2)明显增加,CL_z/F明显降低,AUC_(0～)_t、C_(max)分别升高了1.81、2.13倍。结论葛根芩连汤多次给药较单次给药可提高吡格列酮在大鼠中的总体暴露水平。
AIM To investigate the effects of Gegen Qinlian Decoction on pharmacokinetic behaviors of pioglitazone in rats. METHODS Expermental rats were randomly divided into pioglitazone group and Gegen Qinlian Decoction+pioglitazone group, 6 rats in each group, single intragastric administration(normal saline or 14 g/kg Gegen Qinlian Decoction, followed by 3 mg/kg pioglitazone after 30 min) and multiple intragastric administration(normal saline or 14 g/kg Gegen Qinlian Decoction, once a day, for successive 7 days, followed by normal saline or 14 g/kg Gegen Qinlian Decoction on the 8~(th) day, and 3 mg/kg pioglitazone after 30 min) were given, respectively. After the plasma concentration determination of pioglitazone by LC-MS/MS, the calculation of pharmacokinetic parameters were accomplished. RESULTS After multiple administration, the Gegen Qinlian Decoction+pioglitazone group demonstrated significantly higher AUC, MRT_(0～t), C_(max), T_(max)(P<0.05, P<0.01)and lower CL_z/F(P<0.01) than the pioglitazone group, together with obviously increased MRT_(0～t), t_(1/2), obviously decreased CL_z/F, and 1.81, 2.13 times increase in AUC_(0～t), C_(max), respectively.CONCLUSION The multiple administration of Gegen Qinlian Decoction can improve the overall exposure level of pioglitazone in rats as compared with single administration.
AIM To investigate the effects of Gegen Qinlian Decoction on pharmacokinetic behaviors of pioglitazone in rats. METHODS Expermental rats were randomly divided into pioglitazone group and Gegen Qinlian Decoction+pioglitazone group, 6 rats in each group, single intragastric administration(normal saline or 14 g/kg Gegen Qinlian Decoction, followed by 3 mg/kg pioglitazone after 30 min) and multiple intragastric administration(normal saline or 14 g/kg Gegen Qinlian Decoction, once a day, for successive 7 days, followed by normal saline or 14 g/kg Gegen Qinlian Decoction on the 8~(th) day, and 3 mg/kg pioglitazone after 30 min) were given, respectively. After the plasma concentration determination of pioglitazone by LC-MS/MS, the calculation of pharmacokinetic parameters were accomplished. RESULTS After multiple administration, the Gegen Qinlian Decoction+pioglitazone group demonstrated significantly higher AUC, MRT_(0～t), C_(max), T_(max)(P<0.05, P<0.01)and lower CL_z/F(P<0.01) than the pioglitazone group, together with obviously increased MRT_(0～t), t_(1/2), obviously decreased CL_z/F, and 1.81, 2.13 times increase in AUC_(0～t), C_(max), respectively.CONCLUSION The multiple administration of Gegen Qinlian Decoction can improve the overall exposure level of pioglitazone in rats as compared with single administration.
引文
[1] 黎奔, 陈朝, 段晓红, 等.中西药物相互作用研究进展[J]. 临床医学工程, 2010, 17(6): 148-150.
[2] 王仁云. 贯叶连翘与药物的相互作用[J]. 中成药, 2002, 24(11):875-877.
[3] 毕承华. 中西药相互作用对药物吸收环节的影响[J]. 中国实用医药, 2011,6(36):243-245.
[4] 谭朝丹, 马越鸣, 石荣, 等.黄芩对大鼠体内甲苯磺丁脲药动学的影响[J]. 中成药,2011,33(7):1153-1158.
[5] 金玉琴, 江照云. 中成药与西药同服的利弊分析与药效探索[J]. 中国中药杂志,2008,33(20):2407-2409.
[6] 张庆荣, 赵世芬. 论中西药配伍联用的药代动力学影响[J]. 辽宁中医杂志,2006,33(1):20-21.
[7] 孔雪云, 陈琦, 吴祥, 等.中西药联用相互作用研究进展[J]. 南京中医药大学学报,2018,34(1):5-11.
[8] 潘竞锵, 韩超, 刘惠纯, 等. 葛根芩连汤降血糖作用的实验研究[J]. 中国新药杂志, 2000, 9(3):167-170.
[9] 曾艺鹏,王爱华,胡蕴刚.复方配伍治疗伴湿热兼证糖尿病胃轻瘫的研究[J]. 现代中西医结合杂志, 2006, 15(15): 2023-2024,2140.
[10] 茅彩萍, 顾振纶. 葛根素对糖尿病血管并发症大鼠血浆ET-NO、ET-ANF动态平衡的影响[J]. 中成药, 2004, 26(6):487-489.
[11] She S, Liu W, Li T, et al. Effects of puerarin in STZ-induced diabetic rats by oxidative stress and the TGF-β1/Smad2 pathway[J]. Food Funct, 2014, 5(5): 944-950.
[12] Luo W, Wang C Y, Jin L. Baicalin downregulates Porphyromonas gingivalis lipopolysaccharide-upregulated IL-6 and IL-8 expression in human oral keratinocytes by negative regulation of TLR signaling[J]. PLoS One, 2012, 7(12): e51008.
[13] Waisundara V Y, Siu S Y, Hsu A, et al. Baicalin upregulates the genetic expression of antioxidant enzymes in Type-2 diabetic Goto-Kakizaki rats[J]. Life Sci, 2011, 88(23-24): 1016-1025.
[14] Li Z, Geng Y N, Jiang J D, et al. Antioxidant and anti-inflammatory activities of berberine in the treatment of diabetes mellitus[J]. Evid Based Complement Alternat Med, 2014, 2014: 289264.
[15] Tang L Q, Liu S, Zhang S T, et al. Berberine regulates the expression of E-prostanoid receptors in diabetic rats with nephropathy[J]. Mol Biol Rep, 2014, 41(5):3339-3347.
[16] Wang Y. Attenuation of berberine on lipopolysaccharide-induced inflammatory and apoptosis responses in β-cells via TLR4-independent JNK/NF-κB pathway[J]. Pharm Biol, 2014, 52(4): 532-538.
[17] 杨兴华, 李婧楠, 曾勍婕. 吡格列酮不良反应国内外研究现状[J]. 药品评价, 2012, 9(23): 6-9.
[18] 李章万, 徐秀荣. 色谱分析中生物样品的前处理方法[J]. 药物分析杂志, 1996, 16(1): 55-59.
[2] 王仁云. 贯叶连翘与药物的相互作用[J]. 中成药, 2002, 24(11):875-877.
[3] 毕承华. 中西药相互作用对药物吸收环节的影响[J]. 中国实用医药, 2011,6(36):243-245.
[4] 谭朝丹, 马越鸣, 石荣, 等.黄芩对大鼠体内甲苯磺丁脲药动学的影响[J]. 中成药,2011,33(7):1153-1158.
[5] 金玉琴, 江照云. 中成药与西药同服的利弊分析与药效探索[J]. 中国中药杂志,2008,33(20):2407-2409.
[6] 张庆荣, 赵世芬. 论中西药配伍联用的药代动力学影响[J]. 辽宁中医杂志,2006,33(1):20-21.
[7] 孔雪云, 陈琦, 吴祥, 等.中西药联用相互作用研究进展[J]. 南京中医药大学学报,2018,34(1):5-11.
[8] 潘竞锵, 韩超, 刘惠纯, 等. 葛根芩连汤降血糖作用的实验研究[J]. 中国新药杂志, 2000, 9(3):167-170.
[9] 曾艺鹏,王爱华,胡蕴刚.复方配伍治疗伴湿热兼证糖尿病胃轻瘫的研究[J]. 现代中西医结合杂志, 2006, 15(15): 2023-2024,2140.
[10] 茅彩萍, 顾振纶. 葛根素对糖尿病血管并发症大鼠血浆ET-NO、ET-ANF动态平衡的影响[J]. 中成药, 2004, 26(6):487-489.
[11] She S, Liu W, Li T, et al. Effects of puerarin in STZ-induced diabetic rats by oxidative stress and the TGF-β1/Smad2 pathway[J]. Food Funct, 2014, 5(5): 944-950.
[12] Luo W, Wang C Y, Jin L. Baicalin downregulates Porphyromonas gingivalis lipopolysaccharide-upregulated IL-6 and IL-8 expression in human oral keratinocytes by negative regulation of TLR signaling[J]. PLoS One, 2012, 7(12): e51008.
[13] Waisundara V Y, Siu S Y, Hsu A, et al. Baicalin upregulates the genetic expression of antioxidant enzymes in Type-2 diabetic Goto-Kakizaki rats[J]. Life Sci, 2011, 88(23-24): 1016-1025.
[14] Li Z, Geng Y N, Jiang J D, et al. Antioxidant and anti-inflammatory activities of berberine in the treatment of diabetes mellitus[J]. Evid Based Complement Alternat Med, 2014, 2014: 289264.
[15] Tang L Q, Liu S, Zhang S T, et al. Berberine regulates the expression of E-prostanoid receptors in diabetic rats with nephropathy[J]. Mol Biol Rep, 2014, 41(5):3339-3347.
[16] Wang Y. Attenuation of berberine on lipopolysaccharide-induced inflammatory and apoptosis responses in β-cells via TLR4-independent JNK/NF-κB pathway[J]. Pharm Biol, 2014, 52(4): 532-538.
[17] 杨兴华, 李婧楠, 曾勍婕. 吡格列酮不良反应国内外研究现状[J]. 药品评价, 2012, 9(23): 6-9.
[18] 李章万, 徐秀荣. 色谱分析中生物样品的前处理方法[J]. 药物分析杂志, 1996, 16(1): 55-59.