Clinical Pharmacokinetics of Suramin in Patients With HTLV‐III/LAV Infection
Clinical Pharmacokinetics of Suramin in Patients With HTLV‐III/LAV Infection
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苏拉明在 HTLV-III/LAV 感染患者中的临床药代动力学
DOI：
10.1002/j.1552-4604.1986.tb02897.x
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
C. Myers
中科院分区：
文献类型：
--
作者：
Jerry M. Collins PhD;R. Klecker;R. Yarchoan;H. Lane;A. Fauci;R. Redfield;S. Broder;C. Myers
据报道，苏拉明可抑制多种逆转录病毒的逆转录酶活性，并减少 HTLV-III/LAV（获得性免疫缺陷综合征 (AIDS) 的病原体）的体外感染性和细胞病变效应。作为初步研究的一部分，对苏拉明的临床药代动力学进行了研究，以评估该药物治疗 HTLV-III/LAV 引起的疾病的安全性和有效性。四名患者在五周内静脉注射苏拉明 6.2 克。最后一次给药后，苏拉明的血浆半衰期为 44 至 54 天。这是已报道的用于人类的任何治疗物质中半衰期最长的之一。苏拉明的总血浆水平持续数周高于 100 μg/mL。苏拉明的体外活性在浓度低至 50 μg/mL 时被发现。血浆中未发现代谢物，大部分药物通过尿排泄消除。苏拉明大约 99.7% 与血浆蛋白结合。这些初步临床药代动力学研究的结果可能有助于苏拉明进一步治疗试验的设计，特别是给药频率的选择和肾功能损害的调整。
Suramin has been reported to inhibit the reverse transcriptase activity of a number of retroviruses and to reduce the in vitro infectivity and cytopathic effect of HTLV‐III/LAV, the etiologic agent of acquired immune deficiency syndrome (AIDS). The clinical pharmacokinetics of suramin were investigated as part of a pilot study to evaluate the safety and efficacy of this drug for the treatment of patients with diseases caused by HTLV‐III/LAV. A dose of suramin 6.2 g was given intravenously over a five‐week period to four patients. After the last dose, the plasma half‐life of suramin was 44 to 54 days. This is among the longest half‐lives reported for any therapeutic substance given to humans. Total plasma levels of suramin were greater than 100 μg/mL for several weeks. In vitro activity of suramin was found at concentrations as low as 50 μg/mL. Metabolites were not found in plasma, and urinary excretion accounts for elimination of most of the drug. Suramin is approximately 99.7% bound to plasma proteins. The results from these initial clinical pharmacokinetic studies might assist the design of further therapeutic trials of suramin, especially the selection of frequency of dosing and adjustments for renal impairment.