Pharmacokinetics of levosimendan in pediatric patients evaluated for cardiac surgery.
OBJECTIVE
The objective of the study was to evaluate the pharmacokinetics, hemodynamic effects, and safety of levosimendan in children with congenital heart disease.


METHODS
Open, one group, single-dose study.


METHODS
Cardiac catheter laboratory in a pediatric cardiology department of a university hospital. PATIENTS AND TREATMENTS: 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 microg/kg levosimendan as an intravenous infusion given over 10 mins during the catheterization.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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 microg/kg levosimendan bolus was probably due to a small dose relative to body surface area.
Hospital for Children and Adolescents, Helsinki University Hospital, FIN-00029, Finland. maila.turanlahti@hus.fi
Maila
M
Turanlahti
Talvikki
T
Boldt
Tessa
T
Palkama
Saila
S
Antila
Lasse
L
Lehtonen
Erkki
E
Pesonen
D001682:Biological Availability; D006328:Cardiac Catheterization / Q000379:methods; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D015150:Echocardiography, Doppler; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006330:Heart Defects, Congenital / Q000175:diagnosis* / Q000601:surgery*; D006439:Hemodynamics; D006801:Humans; D006835:Hydrazones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007223:Infant; D007262:Infusions, Intravenous; D008297:Male; D011300:Preoperative Care / Q000379:methods; D011724:Pyridazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000077464:Simendan; D016037:Single-Blind Method; D015996:Survival Rate; D016896:Treatment Outcome
D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan