大鼠髂内动脉灌注甲氨蝶呤时肺及其他主要脏器药物浓度的变化

目的 研究甲氨蝶呤(MTX)髂内动脉灌注时大鼠肺及其他主要脏器药物浓度的变化.方法 选择50只雌性大鼠,随机分为2组,动脉组行股动脉插管、髂内动脉灌注药物,静脉组行股静脉插管、髂内静脉灌注药物.每组分别在5个时间点取血样及组织,利用建立的高效液相色谱方法 分析药物浓度.结果 动脉组大鼠肺、卵巢和子宫的药物浓度-时间曲线下面积(AUC)分别为(3.77±0.28)、(4.40±0.40)、(9.97±0.89)μg·h-1·g-1,静脉组分别为(2.31±0.25)、(3.91±0.19)、(7.65±1.54)μg·h-1·g-1,两组分别比较,差异均有统计学意义(P<0.05).动脉组大鼠血浆、心脏、肾、肝和脾的AUC分别为(6.13±0.53)、(1.90±0.11)、(5.32±0.89)、(14.16±1.96)、(0.76±0.20)μg·h-1·g-1,静脉组分别为(5.79±0.71)、(1.64±0.29)、(5.15±1.69)、(14.29±3.47)、(0.76±0.13)μg·h-1·g-1,两组分别比较,差异均无统计学意义(P>0.05).结论 相比较静脉给药,髂内动脉灌注给药后子宫、卵巢和肺有较高的药物浓度,髂内动脉灌注化疗町以有效地治疗妇科恶性肿瘤的肺转移.

Monitoring of methotrexate concentrations in lung and other tissues of rat through internal iHac artery infusion

Objective To establish the high-performance liquid chromatography(HPLC)method for measuring concentrations of methotrexate(MTX)in rat lung and some other tissues through internal iliac artery infusion.Methods Fifly female Sprague-Dawley rats were included in this study.The rats were randomly assigned to two groups.Methotrexate was injected to group one through internal iliac artery,and was injected to group two through femoral vein.Blood and tissues were collected in each group at 15,30,60.90 and 120 minutes for detection of the drug concentrations with HPLC.Results The area under the concentration time curve(AUC)in rat lung,ovary and uterus in the artery group were separately(3.77±0.28),(4.40±0.40),(9.97±0.89)μg·h-1·g-1,which were significantly different from those of the vein group(2.31±0.25),(3.91±0.19),(7.65±1.54)μg·h-1·g-1;P<0.05].The AUC in the rat plasma,heart,kidney,liver and spleen in the artery group were separately(6.13±0.53),(1.90 ±0.11),(5.32±0.89),(14.16±1.96),(0.76±0.20)μg·h-1·g-1.There were no significant differences from the vein group(5.79±0.71),(1.64±0.29),(5.15±1.69),(14.29 ±3.47),(0.76±0.13)μg·h-1·g-1;P>0.05].Conclusions Through internal iliac artery infusion,there are higher drug concentrations in lung.uterus and ovarian compared to venous injection.The internal-arterial chemotherapy may be used to treat pulmonary metastasis of gynecological tumor.