title: Single- and Multiple-dose Pharmacokinetic, Safety and Tolerability Study of Mildronate Injection in Healthy Chinese Subjects Pharmacokinetic of Mildronate Injection.
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.
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-*Sen University, Yuexiu District, Guang Zhou, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-*Sen University, Yuexiu District, Guang Zhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, the Second Xiangya Hospital, Central South University, Chang Sha, China.
authors.forename: W
authors.initials: W
authors.lastname: Peng
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-*Sen University, Yuexiu District, Guang Zhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: The First Affiliated Hospital, Sun Yat-Sen University, Guang Zhou, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.affiliation: The First Affiliated Hospital, Sun Yat-Sen University, Guang Zhou, China.
authors.forename: H
authors.initials: H
authors.lastname: Tang
authors.affiliation: The First Affiliated Hospital, Sun Yat-Sen University, Guang Zhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liang
authors.affiliation: The First Affiliated Hospital, Sun Yat-Sen University, Guang Zhou, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Ma
authors.affiliation: The First Affiliated Hospital, Sun Yat-Sen University, Guang Zhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.affiliation: The First Affiliated Hospital, Sun Yat-Sen University, Guang Zhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-*Sen University, Yuexiu District, Guang Zhou, China.
authors.forename: G
authors.initials: G
authors.lastname: Zhong
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-*Sen University, Yuexiu District, Guang Zhou, China.
authors.forename: M
authors.initials: M
authors.lastname: Huang
mesh_terms: D000328:Adult; D044466:Asian People; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002681:China; D002853:Chromatography, Liquid; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007267:Injections; D008297:Male; D008763:Methylhydrazines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D002317:Cardiovascular Agents; D008763:Methylhydrazines; C050147:3-(2,2,2-trimethylhydrazine)propionate