氟尿苷在大鼠子宫组织内的分布及药动学研究

 目的研究氟尿苷(FUDR)在大鼠血清及子宫组织内的分布、代谢特征并进一步探讨FUDR与氟尿嘧啶(5FU)转化关系。方法建立了大鼠血清和子宫组织中FUDR及5FU的HPLC测定方法。130只雌性Wistar大鼠随机分组，尾静脉恒速输注FUDR或5FU，并按照设计的时间点断头放血，采集血及子宫组织标本，测定各标本中的FUDR及5FU浓度。考察FUDR在大鼠体内的动力学特征及其与5FU的转化关系，以及FUDR与5FU在大鼠子宫组织的分布特征。结果在本实验的剂量下，FUDR在大鼠体内呈现线性代谢特征，而其代谢物5FU则符合非线性特征。静脉输注时，5FU具有较强的血液/子宫组织穿透能力，其子宫组织5FU浓度(2.19～5.87) μg·g^-1与血液浓度(4.52～5.41) mg·L^-1相当。而输注FUDR时，子宫组织内的FUDR浓度很低，代谢物5FU的浓度(2.53～5.11)μg·g^-1却与输注5FU时的相当，而此时血清5FU浓度(0.47～0.83) mg·L^-1却远低于输注5FU时的血清浓度。结论FUDR具有更强的子宫组织亲和力，静脉输注FUDR后子宫组织内其代谢物5FU的浓度较高。

Studies on pharmacokinetics of floxuridine in rats and its distribution in uterus

OBJECTIVE To study the distribution and metabolism of FUDR in rats,and to explore the in vitro conversion from FUDR to 5FU.METHOD S The HPLC assays for the determination of FUDR and 5FU in serum and uterus were developed,respectively. 130 rats were randomly divided into four dosage groups.Group A,B and C were intravenously infused FUDR of 40,20 and 10 mg·kg·h^-1,respectively.Group D was given 5FU in the same dose as group B. The concentrations of FUDR and 5FU in serum and uterus were determined respectively after collecting samples at certain times post-administration.RESULTS The linear pharmacokinetics of FUDR was found within the experimental dosages,while non-linear pharmacokinetic characteristics was found for the metabolite 5FU after administration of FUDR.The concentrations of 5FU were 2.19～5.87 μg·g^-1 in uterus and 4.52～5.41 mg·L^-1 in serum respectively,indicating strong tissue penetration after infusion of 5FU.The concentrations of FUDR were lower in uterus after infusion. Meanwhile,the concentrations of the metabolite 5FU were 2.53～5.11 μg·g^-1 in uterus and 0.47～0.83 mg·L^-1 in serum respectively.The concentrations of 5FU in serum after administration of FUDR was far lower than that after infusion of 5FU.CONCLUSION FUDR showed strong specific uterus-binding.The high concentrations of 5FU in uterus were found after administration of FUDR.