Disease relevance of Azosemid

• METHODS: Nineteen patients with mild to moderate chronic congestive heart failure received furosemide (40 to 60 mg/day) or azosemide (60 to 90 mg/day) for 5 days in a crossover manner [1].
• The effect of repeated Azosemide infusions (20 mg in 500 ml 5% glucose for one h) on urine volume and electrolyte excretion, and on the activity of the renin-angiotensin-aldosterone system (RAAS) was studied in a group of 15 patients with benign essential hypertension before and during treatment with the beta-adrenergic blocker Trimepranol [2].
• After intravenous administration to rats with PCMC, the total amount of 8-hr urinary excretion of unchanged azosemide was significantly greater (457 versus 305 microg/g body weight), however, the 8-hr urine output (15.3 versus 31.1 ml/g kidney) was not significantly different between control rats and rats with PCMC [3].
• Pharmacokinetics and pharmacodynamics of azosemide after intravenous and oral administration to rats with alloxan-induced diabetes mellitus [4].
• The i.v. and oral doses of azosemide needed to be modified in the acute renal failure patients if the present rat data could be extrapolated to humans [5].

Psychiatry related information on Azosemid

• Effect of water deprivation for 48 hours on the pharmacokinetics and pharmacodynamics of azosemide in rats [6].

High impact information on Azosemid

• Thus azosemide has an estimated bioavailability of 10% [7].
• Azosemide kinetics and dynamics [7].
• Solute free water reabsorption decreased from 3.1 +/- 0.3 to 0.5 +/- 0.9 ml/min after azosemide (p less than 0.05), indicating an effect of azosemide at the ascending limb of the loop of Henle [8].
• METHODS: Dahl salt-sensitive rats fed an 8% NaCl diet from age 8 weeks were divided at age 21 weeks (compensated hypertrophic stage) into three groups: rats treated with furosemide (40 mg/kg/day), those treated with azosemide (80 mg/kg/day) and untreated rats [9].
• Four loop diuretics, i.e., furosemide, piretanide, azosemide, and torasemide, thiazides, probenecid, glibenclamide, and nateglinide inhibited the MCT6-mediated uptake of [3H]bumetanide [10].

Chemical compound and disease context of Azosemid

• Pharmacokinetic and pharmacodynamic changes of azosemide after intravenous and oral administration of azosemide to uranyl nitrate-induced acute renal failure rats [5].

Biological context of Azosemid

• Pharmacokinetics and pharmacodynamics of intravenous azosemide in mutant Nagase analbuminemic rats [11].
• The plasma protein binding of azosemide in control rats and NARs was 97.9 and 84.6%, respectively [11].
• CONCLUSIONS: Furosemide, a short-acting loop diuretic, has a greater influence on heart rate variability and fluid balance than azosemide, a long-acting loop diuretic, in patients with mild to moderate chronic congestive heart failure [1].
• After intravenous administration of azosemide to the AIDRs, the area under the plasma concentration-time curve (AUC) increased considerably (3120 compared with 2520 micrograms min mL-1; P < 0.135) and the total body clearance decreased considerably (3.20 compared with 3.96 mL min-1 kg-1; P < 0.0593) [4].
• The total body clearances of azosemide after intravenous (5 mg kg-1) and intraportal (5 and 10 mg kg-1) administration of the drug to rats were considerably smaller than the cardiac output of rats suggesting that the lung or heart first-pass effect (or both) of azosemide after oral administration of the drug to rats was negligible [12].

Anatomical context of Azosemid

• Evidence is discussed which implies that azosemide inhibits solute transport of the thick ascending limb of the loop of Henle, but may also affect more proximal sites [8].
• Almost complete absorption of azosemide from whole gastrointestinal tract was observed after oral administration of the drug to rats [12].
• Azosemide was stable in human gastric juices and pH solutions ranging from 2 to 13 [12].
• The amount of spiked azosemide remaining after 30 min incubation of 50 mug of azosemide with the 9000 g supernatant fraction of rat small intestine was significantly greater by 100 microg of ascorbic acid (45.3 vs. 40.9 microg) than controls (without ascorbic acid) [13].
• The injection of a small dose of azosemide (0.003 mg/kg) into a renal artery led to a diuretic and natriuretic effect only in the injected kidney [14].

Associations of Azosemid with other chemical compounds

• The effect of renin and aldosterone inhibition by beta-adrenergic blockade on the response to the new diuretic azosemide [2].
• When cells were stimulated with 10(-7) M AVP, low ceiling diuretics (indapamide and trichlormethiazide) did not suppress cAMP formation, while high ceiling diuretics (furosemide and azosemide) significantly suppressed cAMP formation at concentrations of 10(-4) and 10(-3) M [15].
• Mechanism of enhanced bioavailability and diuretic effect of azosemide by ascorbic acid in rats [13].
• However, plasma concentrations of active renin and norepinephrine were significantly higher with furosemide treatment than with azosemide treatment [16].
• We have reported previously that loop diuretics, especially azosemide and ethacrynic acid, may act not only on the AVP receptor site, but also on the post-AVP receptor site in rat renal tubular basolateral membranes [17].

Gene context of Azosemid

• Comparing the loop diuretics, azosemide exerts a similar effect to ethacrynic acid, and they have a more potent antagonistic effect than furosemide with respect to AVP adenylate cyclase activation [18].
• Repeated administration on three consecutive days led, however, to a progressive decrease in the natriuretic effectiveness of Azosemide, associated with an increase in plasma renin activity (from 0.413 o.032 to 1.631 0.438 pmol/l) [2].
• Based on in vitro hepatic microsomal studies, the intrinsic M1 [a metabolite of azosemide; 5-(2-amino-4-chloro-5-sulfamoylphenyl)-tetrazole] formation clearance was significantly faster (67.0% increase) in NARs than that in control rats, and this supports significantly faster CL(NR) in NARs [11].
• The increase in [Cl-]i was reduced by the Na+/K+/2 Cl- -cortransporter-1 (NKCC1) blocker azosemide (100 microM), the CFTR blocker SP-303 (50 microM), the blocker of Ca2+-activated Cl- channels DIDS (100 microM) or the ENaC blocker amiloride (10 microM) [19].
• The glomerular filtration rate and the PAH clearance fell after high doses of azosemide, whilst the renal blood flow measured electromagnetically with a flow probe placed around the renal artery, increased even at high doses [14].

Analytical, diagnostic and therapeutic context of Azosemid

• Separation and analysis of azosemide in urine and in serum by high-performance liquid chromatography [20].
• The pharmacodynamic parameters of azosemide were not significantly different after oral administration of the drug to both groups of rats [21].
• Even though the 4-week and 8-week exercise training caused 53 and 25% increases, respectively, in total cytochrome P450 contents in the liver, exercise training did not cause any changes in the levels of P450 1A2 (which primarily metabolizes azosemide), 2E1 and 3A23 in the liver, as assessed by both Western and Northern blot analyses [22].
• Direct effect of azosemide on the mouse thick ascending limb of Henle's loop was examined by the isolated tubules perfusion technique, and the effect was compared with that of furosemide [23].
• Pharmacokinetics of azosemide in patients with T-drain after cholecystectomy [24].

References