PMID- 21679246
OWN - NLM
STAT- MEDLINE
DCOM- 20130625
LR  - 20161125
IS  - 1472-8206 (Electronic)
IS  - 0767-3981 (Linking)
VI  - 27
IP  - 1
DP  - 2013 Feb
TI  - Nonlinear pharmacokinetic properties of mildronate capsules: a randomized, 
      open-label, single- and multiple-dose study in healthy volunteers.
PG  - 120-8
LID - 10.1111/j.1472-8206.2011.00962.x [doi]
AB  - Mildronate has been used as antianginal drug in parts of Europe for many years, 
      but its pharmacokinetic (PK) properties in humans remain unclear. This study was 
      designed to assess and compare the PK properties of mildronate capsules after 
      single escalating oral dose and multiple doses in healthy Chinese volunteers. 
      Volunteers were randomly assigned to receive a single dose of 250, 500, 1000, 
      1250 or 1500 mg of mildronate capsules. Those who received the 500-mg dose 
      continued on the multiple-dose phase and received 500 mg three times a day for 13 
      days. Plasma drug concentrations were analysed by ultraperformance liquid 
      chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Tolerability 
      was assessed throughout the study. A total of 40 Chinese volunteers were enrolled 
      in the study. No period or sequence effect was observed. Area under the 
      concentration and C(max) were increased proportionally with the dose levels, 
      whereas t(1/2) and V(d)/f were dependent on the dose. Nonlinear PK properties 
      were found at doses of 250-1500 mg. There was an accumulation after multiple-dose 
      administration. No serious adverse events (AEs) were reported in the PK study. 
      The formulation was well tolerated.
CI  - (c) 2011 The Authors Fundamental and Clinical Pharmacology (c) 2011 Societe Francaise 
      de Pharmacologie et de Therapeutique.
FAU - Zhang, Jun
AU  - Zhang J
AD  - Clinical Pharmacy Research Institute, The Second Xiangya Hospital, Central South 
      University, Changsha, China.
FAU - Cai, Li-Jing
AU  - Cai LJ
FAU - Yang, Jian
AU  - Yang J
FAU - Zhang, Qi-Zhi
AU  - Zhang QZ
FAU - Peng, Wen-Xing
AU  - Peng WX
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20110616
PL  - England
TA  - Fundam Clin Pharmacol
JT  - Fundamental & clinical pharmacology
JID - 8710411
RN  - 0 (Capsules)
RN  - 0 (Cardiotonic Agents)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Methylhydrazines)
RN  - 73H7UDN6EC (3-(2,2,2-trimethylhydrazine)propionate)
RN  - EC 1.14.11.1 (gamma-Butyrobetaine Dioxygenase)
SB  - IM
MH  - Adult
MH  - Calibration
MH  - Capsules
MH  - Cardiotonic Agents/administration & dosage/adverse 
      effects/blood/*pharmacokinetics
MH  - China
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/administration & dosage/adverse effects/blood/*pharmacokinetics
MH  - Female
MH  - Half-Life
MH  - Humans
MH  - Limit of Detection
MH  - Male
MH  - Metabolic Clearance Rate
MH  - Methylhydrazines/administration & dosage/adverse effects/blood/*pharmacokinetics
MH  - Reproducibility of Results
MH  - Young Adult
MH  - gamma-Butyrobetaine Dioxygenase/*antagonists & inhibitors
EDAT- 2011/06/18 06:00
MHDA- 2013/06/26 06:00
CRDT- 2011/06/18 06:00
PHST- 2011/06/18 06:00 [entrez]
PHST- 2011/06/18 06:00 [pubmed]
PHST- 2013/06/26 06:00 [medline]
AID - 10.1111/j.1472-8206.2011.00962.x [doi]
PST - ppublish
SO  - Fundam Clin Pharmacol. 2013 Feb;27(1):120-8. doi: 
      10.1111/j.1472-8206.2011.00962.x. Epub 2011 Jun 16.