Antihypertensive effect of diazoxide given intravenously in small repeated doses.
Seven patients with acutely elevated diastolic blood pressure (DBP greater than or equal to 135 mmHg) were treated with repeated injections of diazoxide 1 mg/kg body weight i.v. at 10-min intervals. If the DBP was not reduced to 110 mmHg or less after 5 injections, a dose of 5 mg/kg was given. Serum diazoxide (total and unbound) was determined by high pressure liquid chromatography. In all the patients it was possible to reduce the blood pressure to a satisfactory level (i.e. DBP less than 110 mmHg). The individual plasma diazoxide concentrations necessary to achieve the desired response ranged from 20 to 85 micrograms/ml. A significant correlation was found between the initial venous concentration and the initial reduction in blood pressure (p less than 0.02). A high initial concentration in venous blood was associated with high protein binding ("transport function", p less than 0.05), and so were the elimination half-lives, which ranged from 14.7 to 61.3 h ("depot function", p less than 0.05). It is concluded that the previously recommended therapy of injection of 5 mg/kg as a bolus should be given only to patients who do not respond to small repeated doses.
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D003981:Diazoxide / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D011485:Protein Binding
D003981:Diazoxide