Soike K, Huang J L, Tu J I, Stouffer B, Mitroka J G, Swerdel M, Olsen S, Bonner D P, Tuomari A V, Field A K
Tulane University Regional Primate Research Center, Covington, Louisiana.
J Infect Dis. 1992 Apr;165(4):732-6. doi: 10.1093/infdis/165.4.732.
BV-araU (1-beta-D-arabinofuranosyl-E-5-[2-bromovinyl]uracil) has potent antiviral activity against varicella zoster virus in cell culture and is undergoing clinical evaluation. In the present study, pharmacokinetic parameters and the efficacy of BV-araU against infection with simian varicella virus (SVV) were evaluated in African green monkeys. Pharmacokinetic parameters were determined by analysis of the BV-araU content of sera obtained after oral and intravenous administration to normal monkeys. Peak serum concentrations showed dose proportionality, with the 0.1 mg/kg dose resulting in a peak serum concentration of 0.05 micrograms/ml, the approximately ED50 value for the SVV inoculum in cell culture. BV-araU administered orally twice daily at 0.1 mg/kg for 10 days starting 48 h after intratracheal SVV infection prevented vesicular rash development and suppressed viremia. Effective therapy could be initiated 96 h after infection. Taken together, these results indicate that BV-araU is effective oral therapy at doses that achieve peak serum levels equivalent to the ED50 for SVV in cell culture.
BV-araU（1-β-D-阿拉伯呋喃糖基-E-5-[2-溴乙烯基]尿嘧啶）在细胞培养中对水痘带状疱疹病毒具有强大的抗病毒活性，目前正在进行临床评估。在本研究中，对非洲绿猴评估了BV-araU的药代动力学参数及其抗猴水痘病毒（SVV）感染的疗效。通过分析给正常猴子口服和静脉注射后获得的血清中BV-araU的含量来确定药代动力学参数。血清峰值浓度呈剂量正比关系，0.1mg/kg剂量导致血清峰值浓度为0.05微克/毫升，这大约是细胞培养中SVV接种物的ED50值。在气管内接种SVV感染48小时后，以0.1mg/kg的剂量每日口服两次BV-araU，持续10天，可预防水疱疹的发展并抑制病毒血症。感染96小时后可开始有效治疗。综上所述，这些结果表明，BV-araU在达到与细胞培养中SVV的ED50相当的血清峰值水平的剂量下是有效的口服治疗药物。
