肺癌患者超声雾化吸入5-FU的药动学及肺、癌组织中的浓度

Pharmacokinetic of inhaling fluorouracilum by ultrasonic atomizer and the concentration in lungs and tumour in patients with lung cancer

目的：观察肺癌患者超声雾化吸入５氟尿嘧啶（５ＦＵ）的药动学及肺、癌组织中药物浓度，对超声雾化吸入法与常规用药法进行比较。方法：采用ＨＰＬＣ测定患者血清中的５ＦＵ浓度和手术患者正常肺组织与癌组织中的浓度，对血清药时数据拟合后观察有关的药动学参数。结果：平均吸收半衰期０．１０ｈ，分布和消除半衰期分别为０．１５ｈ和０．３４ｈ，达峰时间０．２３ｈ，峰浓度２．３２μｇ·ｍｌ－１。术前雾化吸入２０ｍｉｎ的患者，术中所取肺组织和癌肿组织中５ＦＵ浓度分别为０．３７μｇ·ｇ－１和０．４４μｇ·ｇ－１。结论：超声雾化吸入５ＦＵ的吸收速度大于口服给药，癌组织内药物浓度较高，提示该给药方法是合理可行的。

OBJECTIVE: To determine the concentrations of fluorouracilum in serum, lungs and tumour in patients was lung cancer after inhaling fluorouracilum by ultrasonic atomizer, and check the method against the conventional methods. METHODS: 10 patients with lung cancer served as targets of the experiment. A high performance liquid chromatography method with a 5 μm Kromasil C18 column 4.6 mm×200 mm and a mobile phase consisted of acetonitrilemthanol0.025 mol·L-1 K2HPO4 solution (10∶40∶50) was used. After fluorouracilum inhaled 250 mg: 10 ml, serum samples were collected at 2, 5, 10, 20, 30, 45, 60, 90, 120, 240 min and tissue samples obtained duing operation. The data obtained were fitted with PKBPN1 pharmacokinetic progarm on a computer. RESULTS: The results showed that the disposion of fluorouracilum was conformed to a twocompartment model with t1/2Ka=0.10 h, t1/2α=0.15 h, t1/2β=0.34 h, tmax=0.23 h and cmax=2.32 μg·ml-1. The concentration of tissue of lung and tumour was 0.37 μg·g-1 and 0.44 μg·g-1. CONCLUSIONS: The assimilate rate for fluorouracilum is fast and the harmful effects are less and light with the inhaling fluorouracilum by ultrasonic atomizer rather than old preparation.