Pharmacodynamics and pharmacokinetics of xipamide in patients with normal and impaired kidney function

The effect of a single oral dose of 40 mg xipamide on urinary excretion of Na+, K+, Cl-, Ca2+ and Mg2+ in healthy subjects and in patients with varying degrees of renal impairment was compared with various conventional diuretics. Xipamide caused marked excretion of Na+ and Cl-, whereas the diuretic produced only moderate kaliuresis; urinary excretion of Ca2+ was increased in proportion to Na+, like the loop diuretics. Xipamide affected electrolyte excretion even in patients with a creatinine clearance below 30 ml/min, as do the loop diuretics, too. Therefore, the pharmacodynamic characteristics of xipamide are more like those of a loop diuretic than of a thiazide. Xipamide was good bioavailable, its t 1/2 beta was 7 h and urinary recovery of the undegraded drug was 40% of the given dose. In renal insufficiency, t 1/2 beta increased from 7 to only 9h, yielding a moderate increase in the AUC. Urinary recovery of the drug was reduced in proportion to the reduction in the creatinine clearance of the patient. Therefore, significant extrarenal elimination of the diuretic must be postulated, which suffices to prevent significant drug accumulation in renal failure.