Phase I, Single-Dose Study to Assess the Pharmacokinetics and Safety of Suramin in Healthy Chinese Volunteers
Guolan Wu, Huili Zhou, Duo Lv, Ruling Zheng, Lihua Wu, Songxia Yu, Jiejing Kai, Nana Xu, Lie Gu, Nanfang Hong, Jianzhong Shentu
Abstract
Purpose: Suramin is a multifunctional molecule with a wide range of potential applications, including parasitic and viral diseases, as well as cancer. Methods: A double-blinded, randomized, placebo-controlled single ascending dose study was conducted to investigate the safety, tolerability, and pharmacokinetics of suramin in healthy Chinese volunteers. A total of 36 healthy subjects were enrolled. All doses of suramin sodium and placebo were administered as a 30-minute infusion. Blood and urine samples were collected at the designated time points for pharmacokinetic analysis. Safety was assessed by clinical examinations and adverse events. Results: After a single dose, suramin maximum plasma concentration (C max ) and area under the plasma concentration–time curve from time zero to the time of the last measurable concentration (AUC last ) increased in a dose-proportional manner. The plasma half-life (t 1/2 ) was dose-independent, average 48 days (range 28– 105 days). The cumulative percentages of the dose excreted in urine over 7 days were less than 4%. Suramin can be detected in urine samples for longer periods (more than 140 days following infusion). Suramin was generally well tolerated. Treatment-emergent adverse events (TEAEs) were generally mild in severity. Conclusion: The PK and safety profiles of suramin in Chinese subjects indicated that 10 mg/kg or 15 mg/kg could be an appropriate dose in a future multiple-dose study. Keywords: suramin, clinical pharmacokinetics, antiviral, safety, drug repurposing