Pharmacokinetic and pharmacodynamic studies of piretanide in rabbits. III. Sodium and potassium excretion under different hydrated conditions.

The diuretic effect of piretanide, one of the loop diuretics, was investigated in three different hydrated conditions, namely well hydrated condition (treatment I), progressive hydropenic condition (treatment II) and complete hydropenic condition (treatment III) in rabbits. Each rabbit received intravenous administration of 1.5 or 15 mg/kg of piretanide and the urine flow rate, the excretion rates of Na and K, plasma concentrations of Na and K, urine osmolarity, plasma concentration of piretanide and urinary excretion of piretanide were determined after administration. The pharmacokinetics of piretanide was not influenced by the hydration state of the body, even in treatment III. The diuretic effect of piretanide evaluated by both urine flow rate (EH2O) and Na+K excretion rate (ENa+K), was significantly affected by the hydration state of the body. The more the hydropenic state was developed, less amounts of urine or electrolytes were excreted. A pharmacokinetic-pharmacodynamic link model which was proposed in the previous paper was applied to the present experimental results. The result indicated that the diuretic effect, even in the complete hydropenic condition (treatment III), was reasonably described by the model, with minor modifications. The time course of the excretion rate of K (EK) was not always in parallel with ENa+K, but was dependent on treatments. We found that the K-fraction, which was known as an indicator of the Na-K exchange reaction in the distal tubule, was quantitatively related to ENa+K, using a simple equation. Accordingly, the time course of EK was also calculated. The result also indicated that time courses of EK were described reasonably well by the model, regardless of treatments and doses.