LC／MS／MS测定头孢克肟在大鼠口腔组织的分布与药代动力学研究

目的测定头孢克肟大鼠尾静脉给药后在其口腔组织的分布并分析其药代动力学特征，为口腔临床用药提供参考依据。方法采用LC／MS／MS法测定头孢克肟给药后在设定时间点采集血液和牙龈、牙髓、咬肌和下颌骨4种口腔组织中的药物浓度。结果血液中的头孢克肟在4．0h左右即达到峰浓度；牙龈、牙髓中药物的分布与同时期血药浓度接近，牙龈内平均浓度约为血液中的1／3；牙髓略低于牙龈组织；咬肌和下颌骨峰浓度出现的时间比血液和牙龈组织的时间晚2h；咬肌中药物的含量均较低，仅为血药浓度的1／5；下颌骨中药物的含量最低，仅为血药浓度的1／6。结论头孢克肟均可分布在牙龈、牙髓、咬肌、下颌骨等口腔组织，浓度大小依次是牙龈、牙髓、咬肌和下颌骨为血浓度的1／6～1／3（0．42～0．84μg/mL），基本可以抑制绝大多数口腔临床引起感染性疾病的菌群，适合联合用药应用于口腔感染性疾病。

Distribution and Pharmacokinetics Analysis for Cefixime in Oral Tissues of Rats Using LC/MS/MS

Objective To analyze the distributions and pharmacokinetic features of cefixime in oral tissues of rats after tail vein administration, so as to provide a reference for its clinical application. Methods Samples from blood, gingiva, dental pup, masseter and mandibular at setting time after application of cefixime were collected, and the drug concentrations in different tissues were measureed by LC/MS/MS. Results Concentration of cefixime in blood reached its peak after about 4 h. Concentrations of cefixime in gingival and dental pup were close to that in blood at the same time, and the mean concentration in gingival was about one third of that in blood, while in dental pup it was a little bit lower than that in gingival. The time for drug concentrations at peaks in masseter and mandibular was later than that in blood and gingival for 2 h, with the concentration in masseter is one fifth of that in blood. The concentration in mandibular was the lowest in all oral tissues, which was only one-sixth of that in blood. Conciusion The distributions of cefixime in oral tissues are investigated, including gingiva, dental pup, masseter and mandibular. The concentrations of cefixime in different tissues in descending sequence are ： gingiva, dental pup, masseter and mandibular, ranging from one sixth to one third （0.42 - 0.84 μg/mL） of that in blood. Therefore, cefixime can inhibit the vast majority of bacteria of oral clinical caused of infectious diseases, presented in this work is suitable for drug combination in infectious diseases of oral cavity.