Novel multivalent effects of pyrazinoylguanidine in patients with azotemia.
In patients with azotemia, urea excretion, urea clearance, and urea/creatinine clearance ratio were increased by pyrazinoylguanidine in a dose-related manner. Urine volume and excretion of sodium greater than chloride greater than potassium tended to increase during administration of pyrazinoylguanidine. Systemic arterial pressure declined while pyrazinoylguanidine was given at 300 or 600 mg b.i.d. for 3 days. At both doses pyrazinoylguanidine reduced plasma renin activity during the first 2 hours. Between days 1 and 3 only the high dose of pyrazinoylguanidine decreased plasma renin activity and plasma aldosterone levels. These findings with pyrazinoylguanidine are consistent with those of secretion of urea in human subjects across the renal tubules and indicate that this process is susceptible to pharmacologic alteration, even in the presence of severe renal insufficiency.
Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey 17033.
K H
KH
Beyer
R T
RT
Gelarden
J E
JE
Vary
L E
LE
Brown
E S
ES
Vesell
D000328:Adult; D000450:Aldosterone / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002986:Clinical Trials as Topic; D003404:Creatinine / Q000378:metabolism; D004573:Electrolytes / Q000378:metabolism; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006146:Guanidines / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000009:adverse effects / Q000494:pharmacology*; D012084:Renin-Angiotensin System / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D014508:Urea / Q000097:blood / Q000378:metabolism; D014511:Uremia / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism
D004573:Electrolytes; D006146:Guanidines; D011719:Pyrazines; D000450:Aldosterone; C056104:2-pyrazinoylguanidine; D014508:Urea; D012964:Sodium; D003404:Creatinine