title: Mildronate treatment alters γ-butyrobetaine and l-carnitine concentrations in healthy volunteers.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
authors.affiliation: Latvian Institute of Organic Synthesis, Riga LV1006, Latvia. ledgars@biomed.lu.lv
authors.forename: Edgars
authors.initials: E
authors.lastname: Liepinsh
authors.forename: Ilze
authors.initials: I
authors.lastname: Konrade
authors.forename: Elina
authors.initials: E
authors.lastname: Skapare
authors.forename: Osvalds
authors.initials: O
authors.lastname: Pugovics
authors.forename: Solveiga
authors.initials: S
authors.lastname: Grinberga
authors.forename: Janis
authors.initials: J
authors.lastname: Kuka
authors.forename: Ivars
authors.initials: I
authors.lastname: Kalvinsh
authors.forename: Maija
authors.initials: M
authors.lastname: Dambrova
mesh_terms: D000328:Adult; D001622:Betaine / Q000031:analogs & derivatives* / Q000097:blood / Q000652:urine; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D002331:Carnitine / Q000097:blood* / Q000652:urine; D004032:Diet; D005260:Female; D006801:Humans; D008297:Male; D008460:Meat; D008763:Methylhydrazines / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008875:Middle Aged; D055815:Young Adult
chemical_list: D002317:Cardiovascular Agents; D008763:Methylhydrazines; D001622:Betaine; C002889:gamma-butyrobetaine; C050147:3-(2,2,2-trimethylhydrazine)propionate; D002331:Carnitine