Pharmacodynamic characterization of posture-related diuretic and saluretic responses to furosemide in humans.
To characterize the postural effect on the pharmacodynamic response to furosemide, seven healthy female subjects received the drug (30 mg i.v.), and the diuretic response and urinary drug excretion were monitored either in the supine or upright posture more than 5 h after dose. Six days later the same procedure was repeated, each subject being assigned to the other posture. Diuresis, chlor- and natriuresis were about 50% greater (P less than .01) in the supine than in the upright posture up to 45 min after dose, despite no significant difference in urinary drug excretion between the postures. Creatinine clearance and fractional sodium excretion were also significantly (P less than .05) greater in the supine posture. Pharmacodynamic analysis with the Emax model revealed that the maximum drug response (Emax) to furosemide in the upright posture was significantly (P less than .01) attenuated by about 65% of that in the supine posture, with no significant difference in either ER50 (urinary drug excretion rate producing 50% of Emax) or slope between the postures. Plasma norepinephrine concentration was significantly (P less than .05) greater, whereas urinary kallikrein excretion was significantly (P less than .05) less in the upright posture. There were no significant differences in blood pressure, plasma renin activity and atrial natriuretic peptide as well as in urinary excretion of prostaglandin E2, dopamine and adenosine between the postures.(ABSTRACT TRUNCATED AT 250 WORDS)
Okaniwa
T
T
Department of Internal Medicine, Tokyo Metropolitan Police Hospital, Japan.
Echizen
H
H
Ishizaki
T
T
Kasao
M
M
Iizuka
T
T
D000328:Adult; D009320:Atrial Natriuretic Factor / Q000097:blood; D002712:Chlorides / Q000652:urine*; D015232:Dinoprostone / Q000652:urine; D004231:Diuresis / Q000187:drug effects*; D005260:Female; D005665:Furosemide / Q000494:pharmacology* / Q000652:urine; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007610:Kallikreins / Q000652:urine; D009638:Norepinephrine / Q000097:blood; D011187:Posture; D012964:Sodium / Q000652:urine*; D013564:Sympathetic Nervous System / Q000187:drug effects
D002712:Chlorides; D005665:Furosemide; D009320:Atrial Natriuretic Factor; D012964:Sodium; D007610:Kallikreins; D015232:Dinoprostone; D009638:Norepinephrine