PMID- 26697890
OWN - NLM
STAT- MEDLINE
DCOM- 20170307
LR  - 20221207
IS  - 2194-9387 (Electronic)
IS  - 2194-9379 (Linking)
VI  - 66
IP  - 5
DP  - 2016 May
TI  - Single- and Multiple-dose Pharmacokinetic, Safety and Tolerability Study of 
      Mildronate Injection in Healthy Chinese Subjects Pharmacokinetic of Mildronate 
      Injection.
PG  - 251-6
LID - 10.1055/s-0035-1569297 [doi]
AB  - 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-infinity 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.
CI  - (c) Georg Thieme Verlag KG Stuttgart . New York.
FAU - Zhao, Z
AU  - Zhao Z
AD  - Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical 
      Sciences, North Campus, Sun Yat-*Sen University, Yuexiu District, Guang Zhou, 
      China.
FAU - Chen, J
AU  - Chen J
AD  - Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical 
      Sciences, North Campus, Sun Yat-*Sen University, Yuexiu District, Guang Zhou, 
      China.
FAU - Peng, W
AU  - Peng W
AD  - Department of Pharmacy, the Second Xiangya Hospital, Central South University, 
      Chang Sha, China.
FAU - Wang, X
AU  - Wang X
AD  - Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical 
      Sciences, North Campus, Sun Yat-*Sen University, Yuexiu District, Guang Zhou, 
      China.
FAU - Chen, Z
AU  - Chen Z
AD  - The First Affiliated Hospital, Sun Yat-Sen University, Guang Zhou, China.
FAU - Tang, H
AU  - Tang H
AD  - The First Affiliated Hospital, Sun Yat-Sen University, Guang Zhou, China.
FAU - Liang, Y
AU  - Liang Y
AD  - The First Affiliated Hospital, Sun Yat-Sen University, Guang Zhou, China.
FAU - Ma, Z
AU  - Ma Z
AD  - The First Affiliated Hospital, Sun Yat-Sen University, Guang Zhou, China.
FAU - Chen, J
AU  - Chen J
AD  - The First Affiliated Hospital, Sun Yat-Sen University, Guang Zhou, China.
FAU - Chen, X
AU  - Chen X
AD  - The First Affiliated Hospital, Sun Yat-Sen University, Guang Zhou, China.
FAU - Zhong, G
AU  - Zhong G
AD  - Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical 
      Sciences, North Campus, Sun Yat-*Sen University, Yuexiu District, Guang Zhou, 
      China.
FAU - Huang, M
AU  - Huang M
AD  - Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical 
      Sciences, North Campus, Sun Yat-*Sen University, Yuexiu District, Guang Zhou, 
      China.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20151223
PL  - Germany
TA  - Drug Res (Stuttg)
JT  - Drug research
JID - 101602406
RN  - 0 (Cardiovascular Agents)
RN  - 0 (Methylhydrazines)
RN  - 73H7UDN6EC (3-(2,2,2-trimethylhydrazine)propionate)
SB  - IM
MH  - Adult
MH  - Asian People
MH  - Cardiovascular Agents/administration & dosage/adverse effects/*pharmacokinetics
MH  - China
MH  - Chromatography, Liquid
MH  - Female
MH  - Healthy Volunteers
MH  - Humans
MH  - Injections
MH  - Male
MH  - Methylhydrazines/administration & dosage/adverse effects/*pharmacokinetics
MH  - Tandem Mass Spectrometry
MH  - Young Adult
EDAT- 2015/12/25 06:00
MHDA- 2017/03/08 06:00
CRDT- 2015/12/25 06:00
PHST- 2015/12/25 06:00 [entrez]
PHST- 2015/12/25 06:00 [pubmed]
PHST- 2017/03/08 06:00 [medline]
AID - 10.1055/s-0035-1569297 [doi]
PST - ppublish
SO  - Drug Res (Stuttg). 2016 May;66(5):251-6. doi: 10.1055/s-0035-1569297. Epub 2015 
      Dec 23.