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Drug Res (Stuttg) 2016; 66(05): 251-256
DOI: 10.1055/s-0035-1569297
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Single- and Multiple-dose Pharmacokinetic, Safety and Tolerability Study of Mildronate Injection in Healthy Chinese Subjects Pharmacokinetic of Mildronate Injection

Z. Zhao
1   Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-*Sen University, Yuexiu District, Guang Zhou, China
,
J. Chen
1   Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-*Sen University, Yuexiu District, Guang Zhou, China
,
W. Peng
2   Department of Pharmacy, the Second Xiangya Hospital, Central South University, Chang Sha, China
,
X. Wang
1   Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-*Sen University, Yuexiu District, Guang Zhou, China
,
Z. Chen
3   The First Affiliated Hospital, Sun Yat-Sen University, Guang Zhou, China
,
H. Tang
3   The First Affiliated Hospital, Sun Yat-Sen University, Guang Zhou, China
,
Y. Liang
3   The First Affiliated Hospital, Sun Yat-Sen University, Guang Zhou, China
,
Z. Ma
3   The First Affiliated Hospital, Sun Yat-Sen University, Guang Zhou, China
,
J. Chen
3   The First Affiliated Hospital, Sun Yat-Sen University, Guang Zhou, China
,
X. Chen
3   The First Affiliated Hospital, Sun Yat-Sen University, Guang Zhou, China
,
G. Zhong
1   Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-*Sen University, Yuexiu District, Guang Zhou, China
,
M. Huang
1   Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-*Sen University, Yuexiu District, Guang Zhou, China
› Author Affiliations
Further Information

Publication History

received 11 October 2015

accepted 25 November 2015

Publication Date:
23 December 2015 (online)

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Abstract

Mildronate is an agent for cardioprotection and neuroprotection. This study aimed to evaluate the pharmacokinetic (PK) profiles, safety and tolerability of mildronate injection after single escalating doses and multiple doses in healthy Chinese subjects. We performed a randomized, open-label, single- and multiple-dose phase I trial including 3 doses of mildronate: 250, 500 and 750 mg. Plasma and urine samples were collected and concentrations of mildronate were analyzed by liquid chromatography-mass spectrometry (LC-MS/MS). PK parameters were calculated using noncompartmental analysis. Safety and tolerability was assessed throughout noting subjects’ vital signs and monitoring adverse events (AEs) and conduct a comprehensive physical examination and laboratory analyses before and after the study. There was no significant difference in C 0, AUC0-t, AUC0-∞ among 3 single-dose groups, whereas T 1/2 had significant statistical difference which may be caused by the inhibition of metabolic enzymes. Single- and multiple-dose intravenous injection of mildronate exhibited linear PK profiles in the range of 250–750 mg. An unconspicuous accumulation phenomenon was found after multiple-dose mildronate administration. No significant gender difference was found and mildronate is primarily excreted by the kidney. No serious AEs were observed. The formulation was safe and well tolerated from 250 to 750 mg.

Key words

healthy Chinese subjects - mildronate injection - pharmacokinetics study - safety - tolerability
 

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