氟尿嘧啶和卡铂周围静脉给药与舌动脉灌注栓塞后药代动力学实验研究

目的研究对比经数字减影血管造影术(DSA)舌动脉介入灌注与经周围静脉给药两种途径抗癌药物在血和组织中浓度的不同变化。方法选4只杂种健康犬,分为两组,一组先静脉给予氟尿嘧啶(Fu)和卡铂(CBP)各75 mg,于给药后10 min、20 min、30 min、1 h、2 h、3 h、5 h、3 d、5 d、8 d静脉取血,于给药后10 min、20 min3、0 min3、d、5 d8、d行舌及颊组织活检,应用高效液相色谱法(HPLC)测定血、组织中药物浓度;3周后行DSA超选择性舌动脉介入灌注抗癌药物栓塞,同上检测血、组织中药物浓度。另一组先行动脉给药,再行静脉给药,余同前组。结果DSA超选择性舌动脉介入灌注抗癌药物栓塞后,血药浓度的衰减比静脉给药变慢,而舌组织中药物浓度显著增加,给药后10、203、0 min舌组织中Fu浓度是静脉用药组的25、20、4倍,颊组织中药物浓度是静脉用药组的25、44、25倍,差异有显著性(F=4.81~52.02,t=2.82~9.75,P<0.01、0.05)。结论术前DSA动脉介入灌注抗癌药物栓塞,能减缓血药浓度的衰减,增加组织中药物浓度。

AN EXPERIMENTAL PHARMACOKINETIC STUDY OF FLUOROURACIL AND CARBOPLATIN BY INTRAVENOUS INJECTION OR INTRA-LINGUAL-ARTERY INFUSION EMBOLIZATION

Objective To measure the concentration change of anticancer drugs in plasma and tissue after transfemoral superselective intra-lingual-arterial infusion embolization under DSA(digital subtraction angiography) and intravenous injection.(Methods Four) dogs were randomly divided into group 1(n=2) and group 2(n=2).In group 1,fluorouracil(Fu) 75 mg and carboplatin(CBP) 75 mg were given intravenously,then transfemoral superselective intra-lingual arterial embolization was done under DSA with Fu 75 mg and CBP 75 mg after three weeks.Venous blood specimens were taken at 10 min,20 min,30 min,1 h,2 h, 3 h,5 h,3 d,5 d,and 8 d,and the lingual tissue and the buccal tissue specimens at 10 min,20 min,30 min,3 d,5 d,and 8 d were collected after drug administration each time.Drug concentrations in plasma and tissue were determined by high-performance liquid chromatography(HPLC).In group 2,the drugs were given intra-arterially first,then intravenously,the rest were the same as group 1. Results The attenuation of erug concentration in plasma after intra-arterial infusion embolization was lower than after intravenous injection.At 10 min,20 min,and 30 min after intra-arterial embolization,the 5-fluorouracil concentration in tissue of the tongue was 25,20 and 4 times that after intravenous injection,and 25,44 and 25 times that after intravenous injection in buccal tissue(F=4.81-52.02;t=2.82-9.75;P<0.01,0.05). Conclusion Intra-arterial infusion embolization with carboplatin and Fu is a better way in treating oral and maxillofacial malignant tumors.