Abstract
The acute effects of a high dose of nafamostat mesilate (NM, 6-amidino-2-naphthyl-p-guanidinobenzoate dimethanesulfonate) were studied in 14 beagles (six controls). NM (10 mg kg-1 hr-1) was continuously administered intravenously for 24 hr. The activated coagulation time was dose-dependently prolonged with NM. Plasma electrolyte imbalances such as hyponatremia, hypochloremia, hyperkalemia and active excretion of sodium into urine were found. Aldosterone levels tended to increase in blood and urine after the administration of NM. Although the precise mechanism of these electrolyte imbalances remains unknown, the increase of aldosterone in blood and urine may have been a secondary response to, rather than the cause of, the electrolyte imbalances. Mean arterial pressure gradually decreased after 5 hr of NM. This hypotension may have reflected the vasodilatation with NM. Although the biochemical and histological studies did not reveal significant side effects, further study will be required to confirm the safety of long-term, high-dose NM. These results indicate that the high-dose NM administration at a rate of 10 mg kg-1 hr-1 during 24 hr has no serious side effects.
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|