吉西他滨及顺铂经动脉、静脉注射后血浆、组织药物浓度的变化

目的：分析不同化疗药物通过动脉及静脉途径注射后血浆及组织内药物浓度的变化情况。方法40只带瘤裸大鼠，随机分为8组，其中4组为动脉组，另4组为静脉组，带瘤裸大鼠分别经动脉及静脉注射吉西他滨及顺铂。于注射后5、10、20、40、80、120、360、720 min采血液标本，注射后10、40、120、720 min取组织标本，以高效液相色谱法测定血浆及肿瘤组织中吉西他滨浓度，ICP-MS法测定血浆及肿瘤组织中的铂含量，计算药代动力学参数。结果经动脉及静脉注射两种药物后，血浆及肿瘤组织中的药物浓度出现规律性变化，其变化过程均可用两室模型来描述。动脉注射两组药物的药代动力学参数与静脉注射的药代动力学参数不同，动脉组注射药物后，血浆药物峰浓度[吉西他滨：（20.84±10.11）μg/mL，顺铂：（15.13±7.12）μg/mL]均低于静脉组[吉西他滨：（28.96±7.02）μg/mL，顺铂：（21.64±9.72）μg/mL]，靶组织内药物峰浓度[吉西他滨：（20.18±9.43）μg/mL，顺铂：（6.98±0.31）μg/mL]均高于静脉组[吉西他滨：（18.19±10.30）μg/mL，顺铂：（3.04±0.11）μg/mL]，靶组织内药物曲线下面积[吉西他滨：（2641±411）μg/（min·mL），顺铂：（6025±870）μg/（min·mL）]均明显高于静脉组[吉西他滨：（1663±568）μg/（min·mL），顺铂：（1780±883）μg/（min·mL）]，差异均有统计学意义（P〈0.05或P〈0.01）。结论动脉注射吉西他滨和顺铂较静脉注射有不同程度的优势，这种优势与药物的药理特性有关。

Concentratin change of chemotherapeutic agents in plasma and tissue af-ter intraarterial and intravenous injection Gemcitabine and Cisplatin

Objective To study the drug concentration change of chemotherapeutic agents in plasma and tissue after arterial and intravenous injection. Methods Gemcitabine and Cisplatin were injected into the 40 mature nude rats with xenografted tumor. The rats were divided into vein injection group and artery injection group randomly. The rats were given Gemcitabine and Cisplatin respectively. Blood samples were collected at 5, 10, 20, 40, 80, 120, 360, 720 min after injection and the tumor tissue specimens were collected at 10, 40, 120, 720 min after injection. Gemcitabine concentration in plasma and tumor tissues were determined by high performance liquid chromatography （HPLC） method, while Cisplatin was determined by inductively coupled plasma-mass spectrometry （ICP-MS）method. The data were analyzed by the pharmacokinetic program. Results Regular concentration change of the three drugs in plasma and tissues were observed after the intravenous and arterial injection, which met the two-compartment model. The pharmacokinetic parameters of the two drugs after intravenous and arterial injection were different. The peak concentration in plasma of artery injection group [Gemcitabine： （20.84±10.11） μg/mL; Cisplatin： （15.13±7.12） μg/mL] were lower than those of the vein injection group [（Gemcitabine： （28.96±7.02） μg/mL; Cisplatin： （21.64±9.72） μg/mL], the peak concentration in tissues of the arterial injections group [Gemcitabine： （20.18±9.43）μg/mL; Cisplatin： （6.98±0.31）μg/mL] were higher than those of the intravenous injection group [Gemictabine： （18.19±10.30） μg/mL; Cisplation：（3.04±0.11） μg/mL], and area under curve （A UC） value [（Gemcitabine： （2641±411） μg/（min·mL）; Cisplatin：（6025±870）μg/（min·mL）], in tissues of the arterial injections group were higher than those of the intravenous injection group [Gemcitabine：（1663±568） μg/（min·mL）; Cisplatin： （1780±883） μg/（min·mL）]. Conclusion Intraarterial