Mildronate treatment alters γ-butyrobetaine and l-carnitine concentrations in healthy volunteers

J Pharm Pharmacol. 2011 Sep;63(9):1195-201. doi: 10.1111/j.2042-7158.2011.01325.x. Epub 2011 Jul 6.


Objectives: In this study, we aimed to investigate the effects of long-term administration of the cardioprotective drug mildronate on the concentrations of l-carnitine and γ-butyrobetaine in healthy volunteers.

Methods: Mildronate was administered perorally, at a dosage of 500mg, twice daily. Plasma and urine samples were collected weekly. Daily meat consumption within an average, non-vegetarian diet was monitored. l-Carnitine, γ-butyrobetaine and mildronate concentrations were measured using the UPLC/MS/MS method.

Key findings: After 4 weeks, the average concentrations of l-carnitine in plasma significantly decreased by 18%. The plasma concentrations of γ-butyrobetaine increased about two-fold, and this effect was statistically significant in both the male and female groups. In urine samples, a significant increase in l-carnitine and γ-butyrobetaine levels was observed, which provides evidence for increased excretion of both substances during the mildronate treatment. At the end of the treatment period, the plasma concentration of mildronate was 20µm on average. There were no significant differences between the effects observed in female and male volunteers. Meat consumption partially reduced the l-carnitine-lowering effects induced by mildronate.

Conclusions: Long-term administration of mildronate significantly lowers l-carnitine plasma concentrations in non-vegetarian, healthy volunteers.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Betaine / analogs & derivatives*
  • Betaine / blood
  • Betaine / urine
  • Cardiovascular Agents / administration & dosage
  • Cardiovascular Agents / blood
  • Cardiovascular Agents / pharmacology*
  • Carnitine / blood*
  • Carnitine / urine
  • Diet*
  • Female
  • Humans
  • Male
  • Meat
  • Methylhydrazines / administration & dosage
  • Methylhydrazines / blood
  • Methylhydrazines / pharmacology*
  • Middle Aged
  • Young Adult


  • Cardiovascular Agents
  • Methylhydrazines
  • Betaine
  • gamma-butyrobetaine
  • 3-(2,2,2-trimethylhydrazine)propionate
  • Carnitine