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Phase I safety, tolerability, and pharmacokinetic studies of tetramethylpyrazine nitrone in healthy Chinese volunteers
Author(s) -
Zhao Caiyun,
Lv Yuan,
Cui Hong,
Zhu Yan,
Wei Minji,
Xia Yahong,
Tian Jihong,
Ma Yan,
Liu Yan,
Zhang Pu,
Wang Xi,
Wu Jing,
Wang Yatai
Publication year - 2021
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21733
Subject(s) - tolerability , pharmacokinetics , tetramethylpyrazine , cmax , medicine , adverse effect , placebo , pharmacology , nitrone , anesthesia , chemistry , pathology , biochemistry , alternative medicine , cycloaddition , catalysis
Background The purpose of this study was to investigate the safety, tolerability and pharmacokinetics of tetramethylpyrazine nitrone (TBN) in healthy Chinese volunteers. Methods A single‐ascending‐dose (SAD) study where 68 subjects were randomized to a single dose of placebo or TBN (50, 100, 200, 400, 700, 1,000, 1,400, or 1,800 mg) through IV infusion over 30 min. A multiple‐ascending‐dose (MAD) study where 24 subjects received TBN twice daily (with 12 hr interval) for total 6.5 days at doses of either 700 or 1,400 mg. Adverse events were recorded and pharmacokinetic samples were collected during the whole study period. Results No serious adverse events were found in the study. All of the observed adverse events, including increased white blood cell (4.4% subjects) and neutrophil counts (4.4% subjects), and decreased hemoglobin levels (4.2% subjects), were laboratory test abnormalities. All the adverse events were mild and tolerable, and returned to normal without any intervention. In the SAD study, linear C max values were observed in the dose interval of 50–1,800 mg. In the MAD study, the average steady‐state concentrations ( C avg.ss ) of TBN in the 700 and 1,400 mg dose group were 2,407 and 5,837 ng/ml, respectively. No drug accumulation was observed in this study. Conclusions TBN is well tolerated in healthy volunteers. Linear C max values were observed in the interval of 50–1,800 mg, and target exposures of TBN were achieved without accumulation after twice daily administration to subjects. (This study has been registered at ChiCTR.org.cn . Identifier: ChiCTR1800016225 and ChiCTR1800019627.)