Pharmacokinetic and pharmacodynamic studies of piretanide in rabbits. IV. Effect of piretanide on the proximal tubules and the loop of Henle under a hydrated condition.
In order to evaluate the effect of piretanide on the renal transport of water and osmotic substances, a clearance study was carried out in well hydrated rabbits. After intravenous bolus administration of piretanide, glomerular filtration rate, proximal tubular clearance and urine flow rate, as well as the pharmacokinetics of piretanide, were determined. A pharmacokinetic and pharmacodynamic link model which was developed in the previous paper was applied to the present experimental results. The results indicated that the effect of piretanide on the renal transport of water and osmotic substances in the hydrated rabbits was reasonably described by the model. The model analysis suggested that the diuretic response to piretanide was attributable to the inhibition of reabsorption of electrolytes in the proximal tubule, as well as in the loop of Henle.
Lu
W
W
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Kakemi
M
M
Koizumi
T
T
D000818:Animals; D001834:Body Water / Q000502:physiology; D004231:Diuresis / Q000187:drug effects; D004232:Diuretics / Q000493:pharmacokinetics / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007671:Kidney Concentrating Ability / Q000187:drug effects; D007684:Kidney Tubules / Q000187:drug effects*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D008138:Loop of Henle / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D009994:Osmolar Concentration; D011817:Rabbits; D013449:Sulfonamides / Q000493:pharmacokinetics / Q000494:pharmacology*
D004232:Diuretics; D013449:Sulfonamides; C015451:piretanide