Biomedical subjects

J Denef

Publications and source records attributed to J Denef.

8 recordsLinked to original sources

PubMed1985

Pharmacological properties of the new potent diuretic torasemide in rats and dogs.

Torasemide, a pyridine-3-sulfonylurea derivative, has potent diuretic activity in rats and dogs. In both species urinary volume and electrolyte excretion increased linearly with the logarithm of the dose, thus resembling the profile of a high ceiling diuretic. The minimum effective dose by oral route was 0.2 mg/kg in the rat and less that 0.1 mg/kg in the dog. Maximal effect was obtained with about 10 mg/kg. Experiments by oral and i.v. routes in the rat indicated that torasemide was equally potent by both oral and parenteral administration. In both rats and dogs, urinary excretions induced by torasemide were similar to those obtained with furosemide. However, for the same natriuretic effect, potassium losses with torasemide were significantly less than with furosemide. On a weight basis, torasemide was 9-40 times more potent than furosemide in the rat and about 10 times in the dog. After oral administration the diuretic effects of torasemide started within 20 min and lasted approximately 2 h in the rat and more than 8 h in the dog. The activity of torasemide was not decreased after a repeated daily oral dose of 10 mg/kg for 15 days in the rat. Torasemide at a daily oral dose of 5 mg/kg for 12 days effectively reduced the arterial blood pressure in desoxycortone induced hypertension in the rat. Besides the diuretic and antihypertensive effects no other significant pharmacological effects were observed with torasemide in the different in vitro and in vivo experiments. Torasemide was practically fully absorbed by the gastrointestinal tract, its bioavailability by oral route ranged from 80 to 100%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Renal effects of the high ceiling diuretic torasemide in rats and dogs.

The mode of action of torasemide was investigated by clearance experiments in dogs and rats. In the dog, torasemide (1 mg/kg i.v.) had no significant effect on glomerular filtration rate (GFR) but increased p-aminohippuric acid (PAH) clearance by 16% (p less than 0.01). In the rat both GFR and PAH clearance were significantly decreased, on an average 8-17%, by torasemide infused in the dose range of 1 to 20 mg/kg i.v. After i.v. injection the onset of diuresis was observed within 5 to 10 min and peak effect within 20 to 40 min in the rat and within 40 to 60 min in the dog. Fractional water and sodium excretions of nearly 25% were obtained in the rat with a dose of 8 mg/kg i.v. At equipotent doses, torasemide and furosemide induced similar diuretic and natriuretic effects in function of time in the rat. In the dog the effects lasted much longer with torasemide than with furosemide. This difference can be related to the longer half-life (about 8 h) of torasemide in the dog. In both species significant differences could be noted between torasemide and furosemide with respect to the time course of their effects on the urinary excretion of potassium. From the first experimental hour on, torasemide proved to be significantly less kaliuretic than furosemide as shown by increased Na/K ratios, during the third experimental hour they reached 20.5 vs 9.9 in the dog and 11 vs 7.5 in the rat with torasemide and furosemide, respectively. In hydropenic dogs, free water reabsorption was significantly reduced with torasemide and osmolar clearance significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

PubMed1985

Effects of the diuretic torasemide on p-aminohippuric acid transport in the rat.

The effect of torasemide, a new diuretic, on p-aminohippuric acid (PAH) transport (TPAH) was studied using renal clearance and micropuncture techniques in anaesthetized rats. In clearance experiments, TPAH and TPAH/glomerular filtration rate (GFR) did not significantly change after i.v. administration of torasemide or furosemide but decreased after probenecid injection. In order to enhance the possibility to demonstrate torasemide and PAH interference, small volumes of [3H]-PAH + [14C]-inulin solutions were directly injected into the peritubular capillary system using calibrated micropipettes. When the concentration of microinjected PAH was less than or equal to 0.6 mmol/l, fractional recovery of [3H]-PAH from the micropunctured kidney was not significantly decreased by the diuretics in contrast to probenecid. When the concentration of microinjected PAH was greater than or equal to 5 mmol/l, fractional recovery of [3H]-PAH from the micropunctured kidney was significantly decreased by torasemide from 252% (control) to 210% (P less than 0.005), by furosemide to 217% (P less than 0.005), and by probenecid to 205% (P less than 0.01). Under these conditions, differential transit times between [3H]-PAH and [14C]-inulin in the micropunctured kidney were decreased from -15 to -4 s in the presence of torasemide (P less than 0.05). They were slightly but not significantly reduced by furosemide and probenecid. These findings suggest interference, at least to some extent, between torasemide and PAH secretion in the rat kidney.

Aminohippuric Acids↗

PubMed1973