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目的:研究布洛芬在大鼠原代培养肝细胞中的代谢情况。方法:建立大鼠肝细胞的分离及原代培养方法,考察肝细胞对布洛芬的代谢情况;采用2步灌流技术并运用胶原酶消化法,分离肝细胞并分别与2.50、5.00、20.00μg·mL-1浓度布洛芬进行悬浮共培养,在不同时间点取样,应用高效液相色谱法测定布洛芬的浓度并计算其它药动学参数。结果:240min内肝细胞活率>80%,能满足代谢要求;布洛芬低、中、高3种浓度药动学数据Ke为(0.0064±0.0011)、(0.0086±0.009)、(0.0091±0.0015)min-1,t1/2为(110.0562±17.16)、(81.3873±9.2815)、(77.9516±12.1355)min;AUC为(272.9287±35.58)、(448.9899±23.0295)、(2157.6777±318.8730)μg·mL·min-1;CLs为(0.0093±0.0011)、(0.0112±0.0005)、(0.0094±0.0014)mL·min-1。结论:利用原代肝细胞培养技术对布洛芬代谢进行研究,可为临床优化治疗、合理用药等方面提供有价值的实验数据。
Objective: To study the metabolism of ibuprofen in rat primary cultured hepatocytes. Methods: The isolation and primary culture of rat hepatocytes were established, and the metabolism of ibuprofen in hepatocytes was investigated. The hepatocytes were separated by 2-step perfusion technique and collagenase digestion, · Ibuprofen at a concentration of mL-1 was co-cultured in suspension and sampled at different time points. The concentration of ibuprofen was determined by HPLC and other pharmacokinetic parameters were calculated. Results: The viability of hepatocytes was> 80% within 240 min, which could meet the metabolic requirements. The pharmacokinetics data of low, medium and high concentrations of ibuprofen Ke were 0.0064 ± 0.0011, 0.0086 ± 0.009, 0.0091 ± 0.0015 ) min-1 and t1 / 2 were (110.0562 ± 17.16), (81.3873 ± 9.2815) and (77.9516 ± 12.1355) min, respectively. The AUC values were (272.9287 ± 35.58), (448.9899 ± 23.0295), (2157.6777 ± 318.8730) μg · mL · Min-1; CLs was (0.0093 ± 0.0011), (0.0112 ± 0.0005), (0.0094 ± 0.0014) mL · min-1. Conclusion: The study of metabolism of ibuprofen using primary hepatocyte culture technique can provide valuable experimental data for clinical optimization and rational drug use.