Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Recombinant Neorudin, a New Anticoagulant Drug in Patients With Acute Coronary Syndrome.

Autor: Liu YB; Beijing Institute of Radiation Medicine, Beijing, China.; Institute of Zhejiang University, Quzhou, Zhejiang, China., Liang Y; Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, China., Liu HC; Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, China., Feng GX; Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, China., Zhou XC; Beijing Institute of Radiation Medicine, Beijing, China.; Institute of Zhejiang University, Quzhou, Zhejiang, China., Zhang L; Beijing Institute of Radiation Medicine, Beijing, China.; The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Zhejiang, China., Zhang XL; Institute of Zhejiang University, Quzhou, Zhejiang, China., Li Q; Beijing Institute of Radiation Medicine, Beijing, China., Ren BY; Beijing Institute of Radiation Medicine, Beijing, China., Xia X; Beijing SH Biotechnology Co., Ltd., Beijing, China., Zhu J; Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, China., Wu CT; Beijing Institute of Radiation Medicine, Beijing, China., Jin JD; Beijing Institute of Radiation Medicine, Beijing, China.
Jazyk: angličtina
Zdroj: Clinical pharmacology in drug development [Clin Pharmacol Drug Dev] 2024 Nov; Vol. 13 (11), pp. 1189-1197. Date of Electronic Publication: 2024 Oct 09.
DOI: 10.1002/cpdd.1478
Abstrakt: This study evaluated the safety, tolerability, pharmacodynamics, and pharmacokinetics of recombinant neorudin (EPR-hirudin [EH]) in patients with acute coronary syndrome (ACS), providing a basis for further therapeutic research. This open-label, single-center, nonrandomized, nonblinded, and noncontrolled trial categorized 24 patients with nonprogressive ACS who met the screening criteria into 3 groups. They received an intravenous injection of neorudin (0.4 mg/kg), followed by an intravenous drip at doses of 0.15, 0.30, and 0.45 mg/kg/h for 3 days in the low-, medium-, and high-dose groups, respectively. The safety, tolerability, pharmacodynamics, and pharmacokinetics of EH were assessed after treatment, indicating that neorudin was safe and well tolerated in nonprogressive ACS. No serious adverse events or clinical composite end points were observed. The activated partial thromboplastin time and thrombin time increased significantly and dose dependently following EH administration across all groups compared to pretreatment values. Conversely, thrombin activity significantly decreased after drug administration but returned to baseline levels shortly after drug withdrawal. Within the administered dose range, neorudin exposure increased with the dose, and its half-life was approximately 2 hours. Neorudin was found to be safe and tolerable for treating patients with nonprogressive ACS, demonstrating therapeutic efficacy at doses up to 0.45 mg/kg/h over a 3-day period.
(© 2024 The Author(s). Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)
Databáze: MEDLINE
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