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A New Practical System for Evaluating the Pharmacological Properties of Uricase as a Potential Drug for Hyperuricemia
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  • A New Practical System for Evaluating the Pharmacological Properties of Uricase as a Potential Drug for Hyperuricemia
  • A New Practical System for Evaluating the Pharmacological Properties of Uricase as a Potential Drug for Hyperuricemia
저자명
Feng. Juan,Li. Xiang,Yang. Xiaolan,Zhang. Chun,Yuan. Yonghua,Pu. Jun,Zhao. Yunsheng,Xie. Yanling,Yuan. Huidong,Bu. Youquan,Liao.
간행물명
Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea
권/호정보
2010년|33권 11호|pp.1761-1769 (9 pages)
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대한약학회
파일정보
정기간행물|ENG|
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이 논문은 한국과학기술정보연구원과 논문 연계를 통해 무료로 제공되는 원문입니다.
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기타언어초록

The use of uricase-deficient mammals to screen formulations of engineered uricases as potential drugs for hyperuricemia involves heavy costs and presents a technical bottleneck. Herein, a new practical system was investigated to evaluate the pharmacological significance of a bacterial uricase based on its ability to eliminate uric acid in plasma in vitro, its pharmacokinetics in vivo in healthy rats, and the modeled pharmacodynamics in vivo. This uricase, before and after modification with the monomethyl ether of poly(ethylene glycol)-5000, effectively eliminated uric acid in vitro in rabbit plasma, but its action was susceptible to xanthine inhibition. After intravenous injection of the modified uricase without purification, a bi-exponential model fit well to uricase activities in vivo in the plasma of healthy rats; the half-life of the modified uricase was estimated without interference from the unmodified uricase leftover in the sample and was nearly 100-fold longer than that of the unmodified uricase. Using a model of the elimination of uric acid in vivo taking into account of uricase pharmacokinetics and xanthine inhibition, modeled pharmacodynamics supported that the half-life of uricase and its susceptibility to xanthine are crucial for the pharmacological significance of uricase. Hence, this practical system is desirable for doing preliminary screening of formulations of engineered uricases as potential drugs for hyperuricemia.