The objective of the study was to evaluate the pharmacokinetics, hemodynamic effects, and safety of levosimendan in children with congenital heart disease.
Open, one group, single-dose study.
Cardiac catheter laboratory in a pediatric cardiology department of a university hospital.
Thirteen children between the ages of 3 months and 7 yrs coming for preoperative cardiac catheterization were enrolled into this study. All children received 12 μg/kg levosimendan as an intravenous infusion given over 10 mins during the catheterization.
Concentrations of levosimendan and its metabolites were determined at specified time points before and after infusion (0–4 hrs). Invasive hemodynamics was evaluated up to 25 mins after the start of the infusion and echocardiography up to 2 hrs after the start of the infusion.
The mean maximum concentration of levosimendan was 59 ± 23 ng/mL in children older than 6 months of age. Levosimendan was rapidly distributed, with a mean half-life of 0.24 ± 0.07 hrs. Mean terminal elimination half-life was 1.6 ± 0.80 hrs. Total plasma clearance for the 10-min infusion was 3.6 ± 1.3 mL/min/kg. Terminal elimination half-life in children aged 3–6 months was slower than in older children, i.e., 2.3 hrs vs. 1.6 hrs. Values of other pharmacokinetic variables were on the same level between the two age groups. The changes in hemodynamic variables were not statistically significant. There were no serious adverse events or unexpected adverse drug reactions during the study.
The pharmacokinetic profile of levosimendan in children with congenital heart disease is similar to that in adult patients with congestive heart failure. The minimal hemodynamic efficacy after the 12 μg/kg levosimendan bolus was probably due to a small dose relative to body surface area.
From the Hospital for Children and Adolescents, Helsinki University Hospital, Finland (MT, TB); Orion Pharma, Espoo, Finland (TP, SA); Helsinki University Hospital (LL); and the University of Lund, Sweden (EP).
The work was performed in the Hospital for Children and Adolescents, Helsinki University Hospital, Finland. Supported, in part, by the Orion Pharma Corporation, Espoo, Finland. The experiments comply with the current laws of Finland.
Address requests for reprints to: Maila Turanlahti, MD, Department of Paediatric Cardiology, Division of Paediatrics, Hospital for Children and Adolescents, University of Helsinki, PO Box 281, FIN-00029 HUS, Finland. E-mail: email@example.com