...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biomolecules & therapeutics >Pharmacokinetics of Uridine Following Ocular, Oral and Intravenous Administration in Rabbits
【24h】

Pharmacokinetics of Uridine Following Ocular, Oral and Intravenous Administration in Rabbits

机译：兔眼，口服和静脉内给药后尿苷的药代动力学

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The pyrimidine nucleoside uridine has recently been reported to have a protective effect on cultured human corneal epithelial cells, in an animal model of dry eye and in patients. In this study, we investigate the pharmacokinetic profile of uridine in rabbits, following topical ocular (8 mg/eye), oral (450 mg/kg) and intravenous (100 mg/kg) administration. Blood and urine samples were serially taken, and uridine was measured by high-performance liquid chromatography-tandem mass spectrometry. No symptoms were noted in the animals after uridine treatment. Uridine was not detected in either plasma or urine after topical ocular administration, indicating no systemic exposure to uridine with this treatment route. Following a single intravenous dose, the plasma concentration of uridine showed a bi-exponential decay, with a rapid decline over 10 min, followed by a slow decay with a terminal half-life of 0.36 +- 0.05 h. Clearance and volume of distribution were 1.8 +- 0.6 L/h/kg and 0.58 +- 0.32 L/kg, respectively. The area under the plasma concentration-time curves (AUC) was 59.7 +- 18.2 ng-hr/ml, and urinary excretion up to 12 hr was approx7.7% of the dose. Plasma uridine reached a peak of 25.8 +- 4.1 ng/ml at 2.3 +- 0.8 hr after oral administration. The AUC was 79.0 +- 13.9 mug centre dot hr/ml, representing approx29.4% of absolute bioavailability. About 1% of the oral dose was excreted in the urine. These results should prove useful in the design of future clinical and nonclinical studies conducted with uridine.
机译：在干眼动物模型和患者中，最近有报道嘧啶核苷尿苷对培养的人角膜上皮细胞具有保护作用。在这项研究中，我们研究了局部眼（8 mg /眼），口服（450 mg / kg）和静脉内（100 mg / kg）给药后尿苷在兔体内的药代动力学特征。连续采集血液和尿液样本，并通过高效液相色谱-串联质谱法测定尿苷。尿苷处理后在动物中未观察到症状。局部眼部给药后，血浆或尿液中均未检测到尿苷，表明该治疗途径未全身性暴露于尿苷。在单次静脉内给药后，尿苷的血浆浓度显示出双指数衰减，在10分钟内迅速下降，随后缓慢衰减，最终半衰期为0.36±0.05小时。间隙和分配体积分别为1.8±0.6L / h / kg和0.58±0.32L / kg。血浆浓度-时间曲线（AUC）下的面积为59.7±18.2 ng-hr / ml，直至12小时的尿排泄量约为剂量的7.7％。口服后2.3±0.8小时血浆尿苷达到25.8±4.1ng / ml的峰值。 AUC为79.0±13.9马克杯中心点hr / ml，约占绝对生物利用度的29.4％。口服剂量的约1％从尿中排出。这些结果将证明在设计尿苷未来临床和非临床研究中很有用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号