Azosemide kinetics and dynamics

Abstract

Azosemide is a loop diuretic that may also affect sodium reabsorption at the proximal tubule. We gave intravenous and oral doses of the drug to normal subjects to examine its kinetic and dynamic parameters. In the fasting state a lag time of absorption of approximately 1 hr was followed by absorption t 1/2s and elimination t 1/2s of approximately 0.75 and 2 2.5 hr. Only 2% of an oral dose was excreted unchanged in the urine. After intravenous dosing the elimination t 1/2 was approximately 2 hr; 20% of a dose was recovered unchanged. Thus azosemide has an estimated bioavailability of 10%. The relationship between urinary azosemide excretion rate ("dose") and natriuretic response follows a sigmoid-shaped curve with a dose inducing half-maximal response of 9.3 +/- 2.6 micrograms/min, whereas it is 69.8, 12.1 and 1 microgram/min for furosemide, piretanide, and bumetanide respectively.

Differences in the Duration of Diuretic Effects and Impact on the Renin-Angiotensin-Aldosterone System of Furosemide in Healthy Dogs

“…However, long-acting loop diuretics differ from furosemide in terms of pharmacological mechanism, oral bioavailability, absorption, affinity and biological half-life [4,5,8,13,20,33]. Thus, direct comparisons of the effects of different loop diuretics should be made with caution.…”

“…Compared with furosemide, azosemide improves ventricular fibrosis and decreases the mortality rate in a rat heart failure model [37]. Thus, long-acting loop diuretics are attractive in chronic management of heart failure.However, pharmacological variability (dosage, absorption, half-life) can lead to differential diuretic effects and activity of the neurohumoral system [4,5,8,13,20,29,33]. In particular, torasemide is known to have anti-aldosteronergic effects [34], and azosemide is known to have anti-arginine vasopressin effects [26].…”

“…However, pharmacological variability (dosage, absorption, half-life) can lead to differential diuretic effects and activity of the neurohumoral system [4,5,8,13,20,29,33]. In particular, torasemide is known to have anti-aldosteronergic effects [34], and azosemide is known to have anti-arginine vasopressin effects [26].…”

Pharmacokinetics and Pharmacodynamics of Intravenous Azosemide in Mutant Nagase Analbuminemic Rats

“…The relationships between log urinary excretion rate of azosemide and urine flow rate (Greven and Heidenreich, 1981) as well as urinary excretion rate of sodium (Brater et al, 1983) in rats (Greven and Heidenreich, 1981) and in humans (Brater et al, 1983) appear to be sigmoidal. The E max and EC 50 were calculated with the WinNonlin program (Scientific Consulting Inc., Cary, NC) using the following Hill equation:…”

Gender differences in pharmacokinetics and pharmacodynamics of azosemide in rats

“…Azosemide [5-(4-chloro-5-sulphamoyl-2-thenylaminophenyl)-tetrazole] is a loop diuretic closely resembling furosemide in its diuretic action [3]. On a molecular weight basis, its diuretic potency in humans was reported to be greater than that of furosemide after intravenous administration [4], but equipotent after oral administration [5]. This could be due to the high first-pass metabolism of azosemide after oral administration [3], and hence its low oral bioavailability (extent) in humans; which ranges from 10 to 19% [4].…”