Tissue distribution and excretion of 5-fluorouracil from indomethacin 5-fluorouracil-1-ylmethylester in rats.
- Author:
Guang-Hou WANG
1
;
Jing WANG
;
Wei QI
;
Yang CHEN
;
Li-Xin SUN
Author Information
1. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Anti-Inflammatory Agents, Non-Steroidal;
metabolism;
pharmacokinetics;
urine;
Antimetabolites, Antineoplastic;
pharmacokinetics;
urine;
Feces;
chemistry;
Female;
Fluorouracil;
pharmacokinetics;
urine;
Indomethacin;
metabolism;
pharmacokinetics;
urine;
Male;
Prodrugs;
pharmacokinetics;
Random Allocation;
Rats;
Rats, Wistar;
Sensitivity and Specificity;
Tissue Distribution
- From:
Acta Pharmaceutica Sinica
2008;43(1):81-85
- CountryChina
- Language:Chinese
-
Abstract:
To study the tissue distribution and excretion of indomethacin 5-fluorouracil-1-ylmethyl ester (IFM) metabolite 5-fluorouracil in rats, an accurate and specific high performance liquid chromatography method for quantifying IFM in rat plasma and tissues was developed. Biological samples were prepared by liquid-liquid extraction and separated on a Diamonsil C18 column (250 mm x 4.6 mm ID, 5 microm). The mobile phase for tissue samples, plasma samples and feces samples were composed of methanol-water-36% acetic acid (3:96.9:0.1, v/v) and the mobile phase for urine samples was a mixture of methanol-water-36% acetic acid (10:89.9:0.1, v/v). The eluate was monitored by UV absorbance at 260 nm. After a single ig dose of 100 mg x kg(-1) IFM in rats, 5-Fu was mainly distributed in stomach, small intestine, and liver. The concentrations of 5-fluorouracil in other tissues and plasma were low. The excretion of 5-Fu in urine and feces amounted to 0.0065% and 0.063% of the dose, respectively. The method is shown to be accurate and specific, and suitable for preclinical pharmacokinetic studies of IFM.
