Population Pharmacokinetics of Levosimendan and its Metabolites OR-1855 and OR-1896 in Critically Ill Adults, Neonates and Infants on Veno-Arterial ECMO

Our data indicate that levosimendan and its metabolites exhibit altered the pharmacokinetics in neonates/infants on VA-ECMO. Although some of these changes may be associated with ECMO, definitive conclusions on causality cannot be drawn, as age-dependent specific physiology and critically ill conditions may also contribute. These findings support the consideration of dose optimisation in this population. In adults, levosimendan pharmacokinetics seem unaffected, although metabolite concentrations appear slightly reduced compared with non-critically ill patients with heart failure.