PHARMACODYNAMICS OF PIRETANIDE, RAMIPRIL, AND THEIR COMBINATION IN VOLUNTEERS WITH NORMAL KIDNEY-FUNCTION

Pharmacodynamic interactions of 6 mg piretanide and 5 mg ramipril and their combination (Arelix ACE) were investigated in a randomized, plac ebo-controlled double-blind crossover study. Sixteen normotensive heal thy volunteers (20 - 27 years) with normal kidney function received in randomized order 4 times a single dose of the substances or placebo, respectively, (in between wash-out phases of 14 days). All volunteers were kept on a standardized diet of about 9 g of NaCl/day and 2 l of f luid/day. Inulin clearance, PAH clearance as well as fractional salidi uresis, urine enzymes and -proteins were controlled for 24 hours after application of the substances. Humoral factors (e.g. renin angiotensi n system, prostaglandins, endothelin) were documented in regular inter vals to examine possible correlations between hemodynamic changes and changes of the salidiuresis profile. There was no adverse interaction between piretanide and ramipril related to diuresis, sodium excretion, and renal hemodynamics (glomerular filtration rare, renal blood flow) . Diuresis and sodium excretion were increased to a comparable degree by the fixed combination, and also by piretanide alone. The single app lication of ramipril had no influence on these parameters. Inulin- and PAH clearance remained stable with placebo, the monosubstances or wit h the combination. No treatment differences between the plasma concent rations of PGE(2), 6-keto-PGF(1 alpha), thromboxane B-2, PGF(2 alpha) or plasma endothelin were found. Therefore, the treatment with the com bination had no negative effects on glomerular filtration rate and ren al blood flow in healthy volunteers and, hence stabilized renal functi on.