Nafamostat mesilate, a kallikrein inhibitor, prevents pain on injection with propofol.

We have examined the preventative effect of nafamostat mesilate, a kallikrein inhibitor, on pain on injection with propofol in a randomized, double-blind study. A control group (n = 110) and a nafamostat (n = 103) group received 5% glucose 0.02 ml kg-1 and nafamostat 0.02 mg kg-1 diluted with 5% glucose, respectively, followed 1 min later by 1% propofol injected at a rate of 200 mg min-1. Pain scores recorded during injection of propofol were significantly less in the nafamostat than in the control group. In another 10 patients, blood concentrations of nafamostat were measured after administration of nafamostat 0.02 mg kg-1 i.v. Mean nafamostat concentration 1 min after injection was 0.1 (SD 0.05) mumol litre-1, which is sufficient to inhibit plasma kallikrein activity. We conclude that pretreatment with nafamostat 0.02 mg kg-1 significantly reduced pain on propofol injection and this effect may be caused by a reduction in kallikrein activity.