Tsai C C, Follis K E, Grant R F, Nolte R E, Bartz C R, Benveniste R E, Sager P R
University of Washington, Regional Primate Research Center, Seattle, Washington.
J Acquir Immune Defic Syndr (1988). 1993 Oct;6(10):1086-92.
The effect of dosing frequency on zidovudine (ZDV) prophylaxis against simian immunodeficiency virus (SIV) infection was examined in long-tailed macaque monkeys (Macaca fascicularis). The results indicate that dosing frequency is extremely important for drug efficacy. The monkeys were divided into three groups based on dosing frequencies of 6-, 8-, or 12-h intervals. All were given a total daily dose of 100 mg/kg of ZDV. The drug was administered subcutaneously starting 24 h before SIV inoculation, and treatment continued for an additional 28 days. With the total daily dose held constant, ZDV was most therapeutic when administered at 12-h intervals, less effective at 8-h intervals, and least effective at 6-h intervals. These results indicate that early ZDV treatment based on infrequent but high dosages may increase the antiretroviral effect of the drug. These findings could serve as a model for ZDV chemoprophylaxis in humans. In cases involving accidental exposure to SIV or human immunodeficiency virus (HIV-1 or HIV-2), immediate, high-dosage therapies may be most therapeutic.
在食蟹猴中研究了给药频率对齐多夫定（ZDV）预防猴免疫缺陷病毒（SIV）感染的效果。结果表明给药频率对药物疗效极为重要。根据每6、8或12小时的给药间隔将猴子分为三组。所有猴子每日齐多夫定总剂量均为100mg/kg。在接种SIV前24小时开始皮下给药，治疗持续另外28天。在每日总剂量保持恒定的情况下，每12小时给药一次时齐多夫定治疗效果最佳，每8小时给药一次效果次之，每6小时给药一次效果最差。这些结果表明基于不频繁但高剂量的早期齐多夫定治疗可能会增强该药物的抗逆转录病毒作用。这些发现可作为人类齐多夫定化学预防的模型。在涉及意外暴露于SIV或人类免疫缺陷病毒（HIV-1或HIV-2）的情况下，立即进行高剂量治疗可能最具治疗效果。
