Additional mechanisms of nafamostat mesilate-associated hyperkalaemia.
OBJECTIVE
Nafamostat mesilate, a potent protease inhibitor, is widely used for the treatment of pancreatitis, disseminated intravascular coagulation and as an anticoagulant in haemodialysis. However, hyperkalaemia associated with nafamostat mesilate has been reported. It is thought to be due to decreased urinary potassium excretion, of the drug suppression of aldosterone secretion, and a direct inhibitory action on the apical Na+ conductance in collecting ducts. We have seen two cases of nafamostat mesilate associated-hyperkalaemia, which indicated that extrarenal potassium imbalance might play a role in inducing hyperkalaemia.


METHODS
To examine the effect of nafamostat mesilate on potassium transport in erythrocytes in vitro, 86RbCl uptake was measured in red blood cells from eight healthy volunteers.


RESULTS
Nafamostat mesilate and a metabolite, 6-amidino-2-naphthol, at concentrations of 10(-4) and 10(-3) M, respectively, significantly, suppressed potassium influx whilst another metabolite, p-guanidino-benzoic acid, had no effect. The inhibitory action of nafamostat mesilate was not affected by various inhibitors.


CONCLUSIONS
Nafamostat mesilate and its metabolite, 6-amidino-2-naphthol, suppressed potassium influx in erythrocytes by inhibition of a Na-K ATPase dependent pathway, which was not inhibited by amiloride, barium, nor by frusemide (furosemide).
Ookawara
S
S
Department of Medicine, Jichi Medical School, Tochigi-ken, Japan.
Tabei
K
K
Sakurai
T
T
Sakairi
Y
Y
Furuya
H
H
Asano
Y
Y
D000328:Adult; D001550:Benzamidines; D001565:Benzoates / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism; D006146:Guanidines / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced*; D066298:In Vitro Techniques; D009284:Naphthols / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011480:Protease Inhibitors / Q000009:adverse effects*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D001550:Benzamidines; D001565:Benzoates; D006146:Guanidines; D009284:Naphthols; D011480:Protease Inhibitors; C023856:4-guanidinobenzoate; C058874:6-amidino-2-naphthol; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; C032855:nafamostat