| Background and Objective In the arterial chemotherapy, the pharmacological properties of chemotherapy drugs can greatly affect the chemotherapy and are the factors of choosing intraarterial chemotherapy drug. The concentration of chemotherapy drug and the time that tumor cell contact with the drug are two important parameters that can conduce the treatment effect. So exploring the ideal compatible point of concentration and time of can optimize the arterial chemotherapy. The aims of this project are to explore the quantitative rules of different chemotherapeutic drugs through vein and artery of rabbits and the impact factors of arterial chemotherapy.Methods Adult female New Zealand rabbits were chosen for experiments. The chemotherapy drugs were given through iliac artery or ear vein. The injection programs were:①fluorouracil (5-Fu) + epirubicin (EPI) with 6 hours continuous infusion;②5- Fu + pirarubicin (THP) with 6 hours continuous infusion (drug combined).③5-Fu with rapid injection;④5-Fu with 6 h continuous infusion (single drug). To the animals with 6h continuous infusion, the blood and uterine tissue samples were collected at different time during the process of infusion. At the end of infusion, the animals were killed and the heart, lung and pelvic lymph nodes were collected. To the animals with rapid injection, the blood and uterine tissue samples were collected at different time after injection. The drug concentrations in plasma and tissues were determined by HPLC methods.Results The change process of 5-Fu in rabbits were similar no mater giving single or combined. EPI and THP had almost no impact on the pharmacokinetics of 5-Fu. In combined administration, the peak concentration and AUC of fluorouracil in plasma for arterial infusion were lower slightly than that for vein infusion. But in uterus tissue, the content and AUC of fluorouracil for artery infusion were 2-3 times higher than that for vein infusion and in the fat tissue of pelvic, these reached 5 times. In plasma, the peak concentration and AUC of epirubicin and pirarubicin for artery infusion were lower slightly than that for vein infusion. In uterus tissue, the content and AUC of epirubicin and pirarubicin for artery infusion were similar to that for vein infusion. In fat tissue of pelvic, the content of pirarubicin for artery infusion was 5 times higher than that for vein infusion. In heart and lung tissues, the content of epirubicin and pirarubicin for artery infusion were 1/2 of that for vein infusion. When single 5-Fu was administrated, in the rapid injection group rabbits, during 40min after the injection, the serum concentration of 5-Fu of vein injection was significantly higher than that of arterial injection, then the differences gradually disappear; the peak serum drug concentrations of arterial injection were 61.69±18.80μg·ml-1, lower than the vein injection (97.92±30.97μg·ml-1) ; the serum drug AUC value of arterial injection was 12.96±4.91μg·h·ml-1, higher than that of vein injection(18.38±7.31μg·h·ml-1); in the uterine tissue, the drug concentration of artery injection was significantly higher than intravenous injection, the difference was maintained to 2h; artery and vein injection, the peak concentrations of 5-Fu in uterus were 60.36±15.50μg·ml-1 and 36.38±12.86μg·ml-1 respectively, the AUC values of 5-Fu in uterus were 40.45±18.25μg·h·ml-1 and 26.42±11.49μg·h·ml-1, the peak concentration and AUC value of arterial injection were significantly higher than those of intravenous injection. In the 6h infusion group animals, at short time after beginning of 6h intravenous infusion, the serum drug concentrations of intravenous infusion became significantly higher than those of arterial injection until the end of the injection, the peak serum concentrations of intravenous and intraaterial infusion were 2.51±1.89μg·ml-1 and 2.03±0.80μg·ml-1 respectively, the AUC values in serum were 10.35±2.52μg·h·ml-1 and 13.41±5.16μg·h·ml-1 respectively; in uterine tissues, the drug concentrations of intraarterial infusion were significantly higher than those of intravenous infusion, the difference run through almost injection process; in intraaterial infusion and intravenous infusion, the peak concentrations in uterine tissues were 4.46±2.01 and 1.24±0.74μg·ml-1 respectively, the AUC values were 17.60±7.26μg·h·ml-1 and 6.44±1.29μg·h·ml-1, the peak concentration and the AUC values of arterial injection were significantly higher than those of intravenous injection. Calculating the ratio of the 5-Fu peak concentration and AUC of intraaterial injection to that of intravenous injection in uterus, the ratios were 1.66μg·ml-1 and 1.53μg·h·ml-1 in rapid injection and the ratios in 6h infusion were 3.60μg·ml-1 and 2.73μg·h·ml-1 times, higher than the priors.Conclusion①In combined administration, 6h continual arterial infusion of fluorouracil, epirubicin and pirarubicin showed some extent advantages to continual vein infusion of these drugs. These advantages depended on the drugs' pharmacological properties, pirarubicin had no advantage to epirubicin in continual arterial infusion..②In single administration, the rapid injection and 6h infusion of 5-Fu through iliac artery have advantages to those through ear vein in increasing the effect extension to target organizations and decreasing the side effects to the other organizations. The 6h arterial infusion is better than the rapid arterial injection. |
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