BIOAVAILABILITY AND PHARMACOKINETIC PARAMETERS FOR 5-ETHYL-2'-DEOXYURIDINE
BIOAVAILABILITY AND PHARMACOKINETIC PARAMETERS FOR 5-ETHYL-2'-DEOXYURIDINE
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DOI：
10.1016/0166-3542(94)90008-6
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发表时间：
1994-12-01
影响因子：
7.6
通讯作者：
WIEBE, LI
中科院分区：
文献类型：
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作者：
CHERAGHALI, AM;KNAUS, EE;WIEBE, LI
在雄性Balb-e小鼠中静脉内（iv）和经口（po）给药以及雄性Sprague-Dawley大鼠中静脉内给药后，测定5-乙基-2 '-脱氧尿苷（EDU）的药代动力学参数。小鼠和大鼠静脉注射100 mg/kg EDU后血药浓度符合二室动力学模型。根据该动力学模型，EDU在小鼠中的分布半衰期非常短，为1.4 +/- 0.7 min，在大鼠中为1.3 +/- 0.1 min。静脉推注后，大鼠中EDU的消除半衰期（18.5 +/- 1.0 min）明显短于小鼠（24.1 +/- 2.9 min）。EDU在小鼠中的平均停留时间（MRT）（25.8 +/- 4.9 min）也显著长于大鼠（11.0 +/- 2.9 min）。然而，EDU的清除率在大鼠和小鼠中相似。尽管EDU在小鼠和大鼠中的生物转化相似，但EDU糖苷键在小鼠中的裂解不如在大鼠中广泛。小鼠口服100 mg/kg EDU后，生物利用度为49%。口服给药后血液中EDU的浓度提供了一室模型的最佳拟合。EDU的最大血液浓度（C-max）为2.4 +/- 0.2 μ g/g血液，在100 mg/kg po给药后达到31.1 +/- 1.2 min（T-max）。口服EDU后5-乙基尿嘧啶（EU）的AUC显著高于静脉注射EDU后（P < 0.05）。这一观察结果表明，EDU通过胃肠道中存在的磷酸化酶和/或通过系统前代谢进行降解。
Pharmacokinetic parameters for 5-ethyl-2'-deoxyuridine (EDU) were determined following intravenous (iv) and oral (po) dosing in male Balb-e mice and iv dosing in male Sprague-Dawley rats. The concentrations of EDU in blood after 100 mg/kg iv bolus injections into mice and rats were consistent with a two compartment kinetic model. Based on this kinetic model, EDU showed a very short distribution half-life of 1.4 +/- 0.7 min in mice and 1.3 +/- 0.1 min in rats. The elimination half-life of EDU in rats following iv bolus injection, was substantially (18.5 +/- 1.0 min) shorter than that in mice (24.1 +/- 2.9 min). The mean residence time (MRT) of EDU was also substantially longer in mice (25.8 +/- 4.9 min) compared to rats (11.0 +/- 2.9 min). However, clearance of EDU was similar in both rats and mice. Although the biotransformation of EDU was similar in mice and rats, cleavage of the EDU glycoside bond was less extensive in mice than in rats. EDU showed a 49% bioavailability in mice after a 100 mg/kg po dose. The concentration of EDU in blood after a po dose provided the best fit to a one compartment model. The maximum blood concentration of EDU (C-max was 2.4 +/- 0.2 mu g/g of blood which attained 31.1 +/- 1.2 min (T-max) after a 100 mg/kg po dose. The AUC of 5-ethyluracil (EU) after a po dose of EDU was significantly higher (P < 0.05) than after an iv dose of EDU. This observation indicates that EDU undergoes degradation by phosphorylases present in the gastrointestinal tract and/or by presystemic metabolism.