Safety and pharmacokinetic evaluation of intravenous vaccinia immune globulin in healthy volunteers
Safety and pharmacokinetic evaluation of intravenous vaccinia immune globulin in healthy volunteers
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DOI：
10.1086/422998
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发表时间：
2004-09-15
影响因子：
11.8
通讯作者：
Leese, PT
中科院分区：
文献类型：
--
作者：
Hopkins, RJ;Kramer, WG;Leese, PT
背景。牛痘免疫球蛋白（VIG）通过肌肉注射途径历来被用于治疗天花疫苗接种的并发症。需要静脉注射VIG制剂来改善耐受性和药代动力学特征。我们进行了两项独立的研究，以评估静脉注射抗牛痘免疫球蛋白制剂（VIGIV）的可行性。第一项研究评估了一种新生产的静脉给药冻干VIG产品（vigv -lyo）的药代动力学和安全性。78名健康志愿者接受了100 mg/kg、200 mg/kg或500 mg/kg剂量的VIGIV-lyo静脉输注。在第二项研究中，我们对33名健康志愿者静脉滴注100 mg/kg的VIGIV液体产品（VIGIV-liq）的安全性进行了评估。静脉给药后目标剂量（100 mg/kg）下VIG的几何平均滴度是肌内注射后预测几何平均滴度的2.5倍（P < 0.001）。vigv -lyo的药代动力学在100 mg/kg至500 mg/kg剂量范围内呈线性。服用200毫克/千克和500毫克/千克剂量的VIGIV-lyo不会导致明显更高的不良事件发生率。观察到的不良事件率与液体产品与冻干产品相当。结论。这两项研究表明，静脉给药VIG耐受性良好，并且比肌肉给药VIG产生更有利的药代动力学特征。
Background. Vaccinia immune globulin (VIG) administered via the intramuscular route has historically been used for the treatment of complications of smallpox vaccination. Intravenous formulations of VIG are required to improve tolerability and pharmacokinetic profile.Methods. We conducted 2 separate studies to evaluate the feasibility of administration of an intravenous formulation of antivaccinia immune globulin ( VIGIV). The first study assessed the pharmacokinetics and safety of a newly manufactured lyophilized VIG product for intravenous administration (VIGIV-lyo). Seventy-eight healthy volunteers received an intravenous infusion of VIGIV-lyo at doses of 100 mg/kg, 200 mg/kg, or 500 mg/kg. In the second study, we evaluated the safety of a liquid product of VIGIV (VIGIV-liq) in 33 healthy volunteers receiving an intravenous infusion of 100 mg/kg VIGIV-liq.Results. The geometric mean titer of VIG at the target dose ( 100 mg/kg) after intravenous administration is 2.5 times higher than the predicted geometric mean titer after intramuscular injection (P < .001). The pharmacokinetics of VIGIV-lyo are linear for doses from 100 mg/kg through 500 mg/kg. Administration of the 200-mg/kg and 500-mg/kg doses of VIGIV-lyo does not result in markedly higher adverse event rates. The adverse event rates observed with the liquid product are comparable to those seen with the lyophilized product. Conclusions. These 2 studies suggest that intravenous administration of VIG is well tolerated and results in a more favorable pharmacokinetic profile than does VIG administered intramuscularly.