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KMID : 0617219920030010017
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Duksung Bulletin Phamaceutical Sciences
1992 Volume.3 No. 1 p.17 ~ p.24
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Pharmacokinetics of 5-fluorouracil after intravenous infusion of 5-fluorouracil-acetic acid-human serum albumin conjugate to rabbits
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Chung, Sang Mok
Yoon, Eun Jeong/Kim, So Hee/Lee, Myung Gull/Lee, Heejoo/Park, Man Ki/Kim, Chong Kook
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Abstract
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The pharmacokinetics of 5-fluorouracil(5-FU)was compared after 30 min intravenous infusion of the same dose (20 mg/kg as 5-FU)of 5-FU(treatment Ⅰ),5-FU-acetic acid(5-FU-AA, treatment Ⅱ)and 5-FU-AA-human serum albumin conjugates (5-FU-AA-HSA, treatment Ⅲ)to rabbits. After post-infusion, plasma levels of 5-FU declined rapidly with a mean half-life of 8.0 min from treatment Ⅰ, however, they were not detected until 10-50 min and the mean plasma concentration of 1㎍/ml was maintained from 3 to 24 h for treatment Ⅲ. It might be possible to maintain constant plasma concentration s of 5-FU for a long period of time by 30min infusion of 5-FU-AA-HSA conjugates instead of tedious time-consuming infusion of 5-FU, The mean values of 24 h AUC(623 vs 1290㎍ min ml^-1)were significantly higher from treatment Ⅲ than that from treatment Ⅰ.5-FU was not detected from treatment Ⅱ nor 5-FU-AA from treatment Ⅲ in both plasma and urine samples. In treatment Ⅱ, 5-FU-AA was eliminated rapidly with a mean apparent terminal half-life of 18.7 min based on urinary excretion rate data. 5-FU was not detected in brain after 30 min intravenous infusion of both 5-FU and 5-FU-AA, however, significan amounts of 5-FU were found in brain after administration of 5-FU-AA-HSA conjugates. The in vitro release of 5-FU from 5-FU-AA-HSA conjugates was increased in the presence of protease or liver homogenates, however, 5-FU was not detected for up to 24 h incubation of 5-FU-AA with the various solutions.
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KEYWORD
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