Spironolactone pharmacokinetics

SungaUa 1, Bartle WR, Walker SE, et al. Spironolactone pharmacokinetics and pharmacodynamics in patients with cirrhotic ascites. Gastroenterology 1992 102 1680-1685. 

Pharmacokinetics Spironolactone is completely absorbed orally and is strongly bound to proteins. It is rapidly converted to an active metabolite, canrenone [KAN ra none]. The action of spironolactone is largely due to the effect of canrenone, which has mineralocorticoid-blocking activity. Spironolactone induces hepatic cytochrome P-450. 

In humans, spironolactone is absorbed readily and is metabolized in the liver to active compounds called canrenones. It is these metabolites that compete with aldosterone for its cytosolic receptor therefore, the maximal natriuretic effect is not observed until 24-48 h after treatment has been initiated. Spironolactone is indicated for the treatment of primary hyperaldosteronism but is also used in refractory edema and in secondary hyperaldosteronism consequent to use of loop or thiazide-type diuretics (Martinez-Maldonado Cordova 1990, Rose 1989, 1991, Wilcox 1991). In one study, the administration of spironolactone via nasogastric tube (1 and 2mg/kg) to ponies more than doubled the urinary excretion of sodium and reduced the urinary excretion of potassium for a period of 72 h, although there was no difference in the volume of urine produced (Alexander 1982). This suggests that spironolactone is a potassium-sparing agent in horses however, to date, no pharmacokinetic studies have been published. 

The AASLD practice guidelines recommend that diuretic therapy be initiated with the combination of spironolactone and furosemide. Spironolactone alone was commonly recommended for initial therapy, but clinical trials have demonstrated a 14-day delay in the onset of action, as well as the development hyperkalemia when spironolactone is used alone. Administering spironolactone in single daily doses is justified based on its pharmacokinetics and helps to improve patient compliance. If tense ascites is present, paracentesis... 

On oral administration, approximately 90% of the dose of spironolactone is absorbed and is significantly metabolized during its first passage through the liver to its major active metabolite, canrenone (see Table 27.2 for their pharmacokinetic properties), which is interconvertible with its canrenoate anion. Canrenone is an antagonist to... 

No pharmacokinetic interaction appears to occur between hydrochlorothiazide and diltiazem or isradipine. Similarly, hydrochlorothiazide and triamterene did not alter nifedipine pharmacokinetics, and spironolactone does not alter felodipine pharmacokinetics. Combinations of diuretics and calcium-channel blockers are used clinically for their additive antihypertensive effects. 

The pharmacokinetics of isradipine and hydrochlorothiazide are not affected by concurrent use, and the pharmacokinetics of nifedipine are not affected by either hydrochlorothiazide or triamterene. Spironolactone 50 mg was found not to affect either the pharmacokinetics or the clinical effects of felodipine. ... 

Janzon K, Edgar B, Lundborg P, Regardh CG. The influence of cimetidine and spironolactone on the pharmacokinetics and haemodynamic effects of felodipine in healthy subjects. Acta Pharmacol Toxicol (Coperih) (1986) 59 (Suppl 4), 98. 

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