Nafamostat has been reported to cause the drug-induced hyperkalemia. Nafamostat has an inhibitory effect on the serine proteases including tissue kallikrein. The study aimed to examine involvement of tissue kallikrein in the nafamostat-induced hyperkalemia.
Seven-week-old male Wistar-Imamichi rats were used. Nafamostat (6～18mg/kg) or amiloride（3mg/kg）, a potassium-sparing diuretic and a positive control, was i.p. administered. Urine and blood were collected 6 h after administration. Potassium and creatinine (Cr) were measured by the ion-electrode and Jaffe methods, respectively. Tissue kallikrein was measured using the synthetic peptide of the substrate.
In the nafamostat group (n=5), serum potassium and urinary potassium and tissue kallikrein were 5～5.3 mmol/L (control group 4.6±0.2, mean±SD, n=4), 0.33～0.58 mmol/mg Cr (0.56±0.14) and 0.02～0.10μmol/mg Cr (0.11±0.04). In the amiloride group (n=3), they were 6.3±0.6 mmol/L (4.7, mean, n=2), 0.28±0.20 mmol/mg Cr (1.02), 0.06±0.01μmol/mg Cr (0.26), respectively. It was suggested that serum potassium increased and urinary potassium and kallikrein decreased in both groups. In the nafamostat group, redness on the peritonea and hemorrhagic ascites were observed.
Nafamostat-induced hyperkalemia may be involved in the sodium channel inhibition. Intraperitoneal findings may be caused by the anticoagulant effect. Further studies are necessary on the i.v. administration of nafamostat.