目的 采用高效液相色譜（HPLC）法測(cè)定小鼠血漿及組織中左氧氟沙星含量，研究桔梗總皂苷對(duì)其藥動(dòng)學(xué)規(guī)律及組織分布的影響。方法 180只昆明小鼠隨機(jī)分為兩組，組Ⅰ為單獨(dú)ig左氧氟沙星78 mg/kg，組Ⅱ?yàn)橥瑫r(shí)ig桔?？傇碥?5 mg/kg與左氧氟沙星78 mg/kg，采用HPLC法測(cè)定給藥5、15、30、45 min及1、1.5、2、4、8 h后的血漿及肝、肺、腎組織樣品中的左氧氟沙星濃度。結(jié)果 血漿中內(nèi)源性物質(zhì)對(duì)待測(cè)物無干擾；血漿及各組織在檢測(cè)濃度范圍內(nèi)呈良好線性關(guān)系（r²>0.999）；方法日內(nèi)和日間精密度、穩(wěn)定性及提取回收率均符合生物樣品檢測(cè)標(biāo)準(zhǔn)；組ⅠAUC_0-t為（143.593±16.56），組ⅡAUC_0-t為（120.339±15.542），與組Ⅰ比較，組Ⅱ的AUC明顯減小，T_1/2Z顯著縮短，T_max明顯延長(zhǎng)，CLz/F顯著增加，C_max及Vz/F無顯著性差異；肝、肺、腎組織中左氧氟沙星濃度均迅速提高并快速消除，肺組織中消除速度最快，肺中AUC減少最為明顯。結(jié)論 合用時(shí)，桔梗總皂苷使左氧氟沙星在小鼠體內(nèi)消除速率明顯加快，肺組織中尤為明顯，故左氧氟沙星在聯(lián)合含有桔梗成分的中藥治療肺部疾病時(shí)，建議分開服用。

Objective To determine the content of levofloxacin in plasma and tissues of mice by high performance liquid chromatography (HPLC), and to study the pharmacokinetics and tissue distribution characteristics after combined with total saponins of Platycodon grandiflorum.Methods 180 Kunming mice were randomly divided into two groups. Group I was ig levofloxacin 78 mg/kg alone, group II was ig platycodon total saponin 65 mg/kg and levofloxacin 78 mg/kg. The concentrations of levofloxacin in plasma and liver, lung and kidney tissues after 5 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 4 h, 8 h were determined by HPLC. Results The endogenous substances in plasma have no interference with the test substance. Plasma and tissues have a good linear relationship within the detection concentration range (r² > 0.999). The intra- and inter-day precision, stability and extraction recovery rate are consistent with biological sample detection standard. Group IAUC_0-t was (143.593 ±16.56), group IIAUC_0-t was (120.339 ±15.542), compared with group I, group II's AUC is significantly reduced, T_1/2Z was significantly shortened, T_max was significantly prolonged, CLz/F was significantly increased, and there was no significant difference between C_max and Vz/F. The concentration of levofloxacin in liver, lung and kidney tissues increased rapidly and fast eliminated. Eliminates the fastest in lung tissue and AUC reduction is most obvious in lung tissue. Conclusion When taken simultaneously, the total saponin of Platycodon grandiflorum significantly accelerated the elimination rate of levofloxacin in mice. Levofloxacin is recommended to be taken separately in combination with traditional Chinese medicine containing Platycodon grandiflorum for the treatment of lung diseases.

國(guó)家自然科學(xué)基金國(guó)際合作與交流項(xiàng)目（81761168039）