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KMID : 0369820040340030161
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Jorunal of Korean Pharmaceutical Sciences
2004 Volume.34 No. 3 p.161 ~ p.168
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Stability of 5-FU and Tegafur in Biological Fluids of Rats
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장지현/Jang JH
박종국/강진형/정석재/심창구/구효정/Park JK/Kang JH/Chung SJ/Shim CK/Kuh HJ
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Abstract
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5-Fluorouracil (5-FU) is an antimetabolite anticancer agent active against many types of solid tumors. Tegafur (TF), a prodrug of 5-FU, is frequently used in combination with uracil as dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine. We studied the stability of 5-FU and TF in biological fluids of rats and determined their bioavailability (BA) and excretion into bile, and urine. The drug concentrations were analyzed by an HPLC method. At room temperature, there was a 14-30% decrease in the concentration of 5-FU and TF in bile, urine, and plasma specimen at 10 and 100 μg/ml over 240 min. No significant difference was noted among the sample types or between two different concentrations of 10 and 100 μg/ml. The decrease in drug concentration was significantly less in samples kept on ice (6-12%) for both drugs. These data indicate that biological fluid samples containing 5-FU or TF in plasma, urine, or bile should be placed on ice during the sample collection. Following these storage guidelines, samples were collected after administration 50 ㎎/㎏ of each drug via i.v. or oral route. BA was 1.5 folds greater for TF (60%) than that of 5-FU (42%). Approximately 0.52 and 3.3% of the i.v. doses of 5-FU and TF was excreted into bile, respectively. Renal clearance of 5-FU was about 16% of its total body clearance. These results suggest that instability of 5-FU and TF in biological fluids should be considered in pharmacokinetic or pharmacogenomic studies.
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KEYWORD
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5-FU, Tegafu, Stability, Bioavailability
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