Xipamide (CAS 14293-44-8) shows structural features comparable with the
thiazide- as well as the class of
loop diuretics. According to earlier findings this
diuretic, in contrast to the
thiazides, should not decrease the glomerular filtration rate (GFR) and be effective even in patients with advanced
renal failure. Therefore recently the question, which class of
diuretics xipamide should be related to, has been increasingly discussed. In order to solve this issue, the
diuretic effect of
xipamide was assessed in healthy volunteers once without and once under strict water and
salt restriction. Additionally, changes in GFR were monitored by means of measurement of the
creatinine clearance. Kinetic parameters were determined in plasma and urine; further, in patients with
liver cirrhosis, renal elimination kinetics of the
diuretic were correlated with the concentration of direct plasma
bilirubin, as a marker of
cholestasis, at the beginning of a treatment with
xipamide, 40 mg qd. The investigations proved that
xipamide, like a typical
thiazide diuretic, gives rise to a temporary decrease in GFR of about 30 %, provided the renin-angiotensin-aldosterone system of the volunteer is activated by previous
salt and water restriction.
Xipamide leads to an increase of K+ and Mg2+ excretion, but to a decrease of Ca2+ excretion in urine, a charactaristical feature of the
thiazide-like
diuretics. The correlation between Na+ excretion and
drug excreted in urine over time showed a functional graph that is characteristic for a "low ceiling"
thiazide diuretic. In patients with
renal failure FE(Na) was increased when related to the GFR-adjusted drug excretion rate, whereas it was diminished in conditions with decreased effective circulating volume like in
liver cirrhosis with
ascites. It could be shown that the elimination kinetics of
xipamide are determined by renal drug clearance, which proportionally decreases with GFR. In patients with
liver failure, a decrease of non-renal drug clearance went along with an increase in urinary drug excretion. The amount of
drug excreted in urine (Ae) proportionally increased with the concentration of the patients' direct plasma
bilirubin. Thus, from a pharmacological as well as clinical point of view
xipamide acts like a
thiazide diuretic. As could be shown for other
thiazides some time ago,
xipamide is effective not only in patients with
cardiovascular diseases, but also in those with advanced
renal failure.