Xipamide

Xipamide is a sulfonamide diuretic drug marketed by Eli Lilly under the trade names Aquaphor (in Germany) and Aquaphoril (in Austria). It is used for the treatment of oedema and hypertension.
Mechanism of action.
Like the structurally related thiazide diuretics, xipamide acts on the kidneys to reduce sodium reabsorption in the distal convoluted tubule. This increases the osmolarity in the lumen, causing less water to be reabsorbed by the collecting ducts. This leads to increased urinary output. Unlike the thiazides, xipamide reaches its target from the peritubular side (blood side).
Additionally, it increases the secretion of potassium in the distal tubule and collecting ducts. In high doses it also inhibits the enzyme carbonic anhydrase which leads to increased secretion of bicarbonate and alkalizes the urine.
Unlike with thiazides, only terminal kidney failure renders xipamide ineffective.
Uses.
Xipamide is used for
Pharmacokinetics.
After oral administration, 20 mg of xipamide are resorbed quickly and reach the peak plasma concentration of 3 mg/l within an hour. The diuretic effect starts about an hour after administration, reaches its peak between the third and sixth hour, and lasts for nearly 24 hours.
One third of the dose is glucuronidized, the rest is excreted directly through the kidney (1/3) and the faeces (2/3). The total plasma clearance is 30-40 ml/min. Xipamide can be filtrated by haemodialysis but not by peritoneal dialysis.
Dosage.
Initially 40 mg, it can be reduced to 10–20 mg to prevent a relapse.
The lowest effective dose is 5 mg. More than 60 mg have no additional effects.
Interactions.
Combinations requiring special precautions.
The product information requests special precautions for these combinations:
Banned use in sport.
On 17 July 2012, cyclist Fränk Schleck was removed from the Tour de France by his team RadioShack-Nissan after his A-sample returned traces of xipamide.