OBJECTIVE: To study the distribution and metabolism of FUDR in rats, and to explore the in vitro conversion from FUDR to 5FU. METHODS: 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.
|Number of pages||5|
|Journal||Chinese Pharmaceutical Journal|
|State||Published - 1 Mar 2003|