Wang Rui, Yang Yuqian, Zhou Tong, Zou Bingjie, Ding Li
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 211198, China.
Jiangsu Nhwa Pharmaceutical Co., Ltd., Xuzhou 221400, China.
Pharmaceuticals (Basel). 2025 Jul 21;18(7):1079. doi: 10.3390/ph18071079.
: (R)-ketamine hydrochloride injection is a novel, rapid-acting antidepressant for the treatment of treatment-resistant depression. The aim of this study was to assess the pharmacokinetics, safety, and tolerability of (R)-ketamine hydrochloride injection in healthy Chinese subjects following ascending single intravenous doses ranging from 10.0 mg to 180 mg. : This randomized, double-blind, placebo-controlled study was conducted in 50 healthy male and female Chinese subjects after single ascending doses of (R)-ketamine hydrochloride injection (10.0, 30.0, 60.0, 120, and 180 mg). Ten subjects (including two subjects treated with a placebo) were included in each dose cohort. Pharmacokinetic characteristics, safety, and tolerability profiles of the study drug were evaluated. After the intravenous doses administered from 10.0 mg to 180 mg of (R)-ketamine hydrochloride injection to the subjects, the C and AUC values for both (R)-ketamine and its metabolite (R)-norketamine in the subjects increased approximately proportionally to the doses. The average peak plasma concentration levels at the five dose cohorts ranged from 56.0 to 1424 ng/mL and 27.7 to 491 ng/mL for (R)-ketamine and (R)-norketamine, respectively. The adverse events of (R)-ketamine hydrochloride injection were temporary and recovered spontaneously without treatment. : In summary, (R)-ketamine hydrochloride injection was safe and well tolerated in healthy Chinese subjects. The clinical study results laid a foundation for the further clinical studies of (R)-ketamine hydrochloride injection in patients.
（R）-盐酸氯胺酮注射液是一种用于治疗难治性抑郁症的新型速效抗抑郁药。本研究的目的是评估（R）-盐酸氯胺酮注射液在健康中国受试者中静脉注射剂量从10.0毫克递增至180毫克后的药代动力学、安全性和耐受性。：这项随机、双盲、安慰剂对照研究在50名健康中国男性和女性受试者中进行，受试者单次递增剂量注射（R）-盐酸氯胺酮注射液（10.0、30.0、60.0、120和180毫克）。每个剂量组纳入10名受试者（包括2名接受安慰剂治疗的受试者）。评估了研究药物的药代动力学特征、安全性和耐受性。在向受试者静脉注射10.0毫克至180毫克的（R）-盐酸氯胺酮注射液后，受试者体内（R）-氯胺酮及其代谢物（R）-去甲氯胺酮的C和AUC值随剂量增加大致呈比例增加。五个剂量组的平均血浆峰浓度水平，（R）-氯胺酮为56.0至1424纳克/毫升，（R）-去甲氯胺酮为27.7至491纳克/毫升。（R）-盐酸氯胺酮注射液的不良事件是暂时的，未经治疗可自行恢复。：总之，（R）-盐酸氯胺酮注射液在健康中国受试者中安全且耐受性良好。临床研究结果为（R）-盐酸氯胺酮注射液在患者中的进一步临床研究奠定了基础。
