{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T01:07:13Z","timestamp":1790989633744,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,1,10]],"date-time":"2017-01-10T00:00:00Z","timestamp":1484006400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Latvian State Research Program BIOMEDICINE"},{"name":"InnovaBalt"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Meldonium (3\u2010(2,2,2\u2010trimethylhydrazinium)propionate) is the most potent clinically used inhibitor of organic cation transporter 2 (\n                    <jats:styled-content style=\"fixed-case\">OCTN<\/jats:styled-content>\n                    2). Inhibition of\n                    <jats:styled-content style=\"fixed-case\">OCTN<\/jats:styled-content>\n                    2 leads to a decrease in carnitine and acylcarnitine contents in tissues and energy metabolism optimization\u2010related cardioprotective effects. The recent inclusion of meldonium in the World Anti\u2010Doping Agency List of Prohibited Substances and Methods has raised questions about the pharmacokinetics of meldonium and its unusually long elimination time. Therefore, in this study, the rate of meldonium washout after the end of the treatment was tested with and without administration of carnitine, \u03b3\u2010butyrobetaine (\n                    <jats:styled-content style=\"fixed-case\">GBB<\/jats:styled-content>\n                    ) and furosemide to evaluate the importance of competition for\n                    <jats:styled-content style=\"fixed-case\">OCTN<\/jats:styled-content>\n                    2 transport in mice. Here, we show that carnitine and\n                    <jats:styled-content style=\"fixed-case\">GBB<\/jats:styled-content>\n                    administration during the washout period effectively stimulated the elimination of meldonium.\n                    <jats:styled-content style=\"fixed-case\">GBB<\/jats:styled-content>\n                    induced a more pronounced effect on meldonium elimination than carnitine due to the higher affinity of\n                    <jats:styled-content style=\"fixed-case\">GBB<\/jats:styled-content>\n                    for\n                    <jats:styled-content style=\"fixed-case\">OCTN<\/jats:styled-content>\n                    2. The diuretic effect of furosemide did not significantly affect the elimination of meldonium, carnitine and\n                    <jats:styled-content style=\"fixed-case\">GBB<\/jats:styled-content>\n                    . In conclusion, the competition of meldonium, carnitine and\n                    <jats:styled-content style=\"fixed-case\">GBB<\/jats:styled-content>\n                    for\n                    <jats:styled-content style=\"fixed-case\">OCTN<\/jats:styled-content>\n                    2\u2010mediated transport determines the pharmacokinetic properties of meldonium. Thus, due to their affinity for\n                    <jats:styled-content style=\"fixed-case\">OCTN<\/jats:styled-content>\n                    2,\n                    <jats:styled-content style=\"fixed-case\">GBB<\/jats:styled-content>\n                    and carnitine but not furosemide stimulated meldonium elimination. During long\u2010term treatment,\n                    <jats:styled-content style=\"fixed-case\">OCTN<\/jats:styled-content>\n                    2\u2010mediated transport ensures a high muscle content of meldonium, while tissue clearance depends on relatively slow diffusion, thus resulting in the unusually long complete elimination period of meldonium.\n                  <\/jats:p>","DOI":"10.1111\/bcpt.12729","type":"journal-article","created":{"date-parts":[[2016,12,17]],"date-time":"2016-12-17T11:01:37Z","timestamp":1481972497000},"page":"450-456","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Carnitine and \u03b3\u2010Butyrobetaine Stimulate Elimination of Meldonium due to Competition for OCTN2\u2010mediated Transport"],"prefix":"10.1111","volume":"120","author":[{"given":"Edgars","family":"Liepinsh","sequence":"first","affiliation":[{"name":"Latvian Institute of Organic Synthesis Riga 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