Journal of Pharmaceutical Investigation

The Korean Society of Pharmaceutical Sciences and Technology (한국약제학회)
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Stability of 5-FU and Tegafur in Biological Fluids of Rats

흰쥐 생체시료 중 5-플루오로우라실 및 테가푸르의 안정성

  • Jang, Ji-Hyun (Research Institute of New Drug Development, Catholic Research Institutes of Medical Science) ;
  • Park, Jong-Kook (Research Institute of New Drug Development, Catholic Research Institutes of Medical Science) ;
  • Kang, Jin-Hyoung (Division of Medical Oncology, College of Medicine, The Catholic Univ of Korea) ;
  • Chung, Suk-Jae (College of Pharmacy, Seoul National University) ;
  • Shim, Chang-Koo (College of Pharmacy, Seoul National University) ;
  • Kuh, Hyo-Jeong (Research Institute o0f New Drug Development, Catholic Research Institutes of Medical Science)
  • 장지현 (가톨릭대학교 의과학연구원 신약개발연구소) ;
  • 박종국 (가톨릭대학교 의과학연구원 신약개발연구소) ;
  • 강진형 (강남성모병원 혈액종양내과) ;
  • 정석재 (서울대학교 약학대학) ;
  • 심창구 (서울대학교 약학대학) ;
  • 구효정 (가톨릭대학교 의과학연구원 신약개발연구소)
  • Published : 2004.06.20
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Abstract

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 $100\;{\mu}g/ml$ over 240 min. No significant difference was noted among the sample types or between two different concentrations of 10 and $100{\mu}g/ml$. 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 mg/kg 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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References

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