The aim of the present study is to elucidate the pharmacokinetics of nafamostat mesilate (FUT-175) under moderate hypothermic cardiopulmonary bypass (CPB). Using cases of open heart surgery, we measured blood FUT-175 concentration in CPB by combined use of heparin and FUT-175. Arterial and venous FUT-175 concentrations showed no significant difference 10, 30, and 60min following the start of FUT-175 administration,
in vivo metabolism was shown to be remarkably depressed. Intra-circuit and atrial blood FUT-175 concentrations also showed no significant difference, and HPO-25H artificial lung intra-circuit adsorption on FUT-175 was no noted. Intravenous FUT-175 concentration was increased dose-dependently, being about 2.5-4 fold higher for the group of FUT-175, 2.0mg/kg/h continuous administration than the group of 1.5mg/kg/h administration. For the former group, venous blood FUT-175 concentration under moderate hypothermia was increased with time, being 1, 800 and 3, 650ng/ml 10 and 60min following the start of CPB, respectively, and began to be decreased in process of rewarming, being decreased by 67% 10min following the withdrawal.
View full abstract