不同给药方式在大鼠内对利巴韦林的药代动力学和组织分布的影响

目的：利用HPLC-QqQ-MS多反应监测（multiple reaction monitoring, MRM）技术检测方法探究口服和呼吸道给药方式对利巴韦林药代动力学及组织分布情况的影响。方法：实验建立了检测利巴韦林的高灵敏度液质联用分析方法，经过了线性、专属性、回收率、准确度、精密度的考察。用建立的方法对口服和呼吸道给药两种方式的药代动力学和组织分布情况进行考察。结果：呼吸道给药0～72 h血药浓度较高，药物吸收较快，呼吸道给药Cmax（46.1±10.6） μg/L和AUC(0-t)（276±68） μg·L-1·h显著性高于口服给药Cmax（8.9±3.8）μg/L和AUC(0-t)（142±63） μg·L-1·h。组织分布结果表明，呼吸道给药肺组织利巴韦林含量明显高于口服给药，同时呼吸道给药肝脏组织含量较低。 结论：与口服给药相比，呼吸道给药具有较高的血药浓度，及在肺组织含量较高，揭示了吸入给药的组织靶向作用。HPLC-QqQ-MS检测方法简单有效、准确度高、重复性好、可用于大鼠血浆，组织利巴韦林的含量测定。

Effects of different administration methods on the pharmacokinetics and tissue distribution of ribavirin in rats

AIM: To establish a HPLC QqQ MS with multiple reaction monitoring (MRM) method for pharmacokinetics and tissue distribution study of ribavirin by oral and respiratory administration. METHODS: The experiment established a high sensitivity LC MS analytical method for the detection of ribavirin, and the linearity, specificity, recovery, accuracy, and precision were investigated. The established methods were used to investigate the pharmacokinetics and tissue distribution of the oral and respiratory administration methods. RESULTS: The concentration of drugs in the blood through respiratory tract administration is higher, and the drug absorption is faster. Respiratory tract administration Cmax(46.1±10.6) μg/L and AUC(0 t)(276±68) μg·L 1·h are significantly higher than oral administration Cmax(8.9±3.8) μg/L and AUC(0 t)(142±63) μg·L 1·h. The tissue distribution results showed that the content of ribavirin in lung tissue of respiratory tract administration was significantly higher than that of oral administration, and the metabolism time was longer.CONCLUSION: Compared with oral administration, respiratory tract administration has higher blood drug concentration and higher content in lung tissue, revealing the tissue targeting effect of inhaled administration. The HPLC QqQ MS detection method is simple, effective, accurate, and reproducible, which can be applied to the determination of ribavirin in rat plasma and tissue.