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.
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.
Authors: E Liepinsh; M Makrecka-Kuka; J Kuka; R Vilskersts; E Makarova; H Cirule; E Loza; D Lola; S Grinberga; O Pugovics; I Kalvins; M Dambrova Journal: Br J Pharmacol Date: 2015-01-12 Impact factor: 8.739
Authors: Chikara Otsubo; Sivakama Bharathi; Radha Uppala; Olga R Ilkayeva; Dongning Wang; Kevin McHugh; Ye Zou; Jieru Wang; John F Alcorn; Yi Y Zuo; Matthew D Hirschey; Eric S Goetzman Journal: J Biol Chem Date: 2015-08-03 Impact factor: 5.157
Authors: P A Levashov; D A Matolygina; E D Ovchinnikova; D L Atroshenko; S S Savin; N G Belogurova; S A Smirnov; V I Tishkov; A V Levashov Journal: Acta Naturae Date: 2017 Apr-Jun Impact factor: 1.845