The pharmacokinetics of spironolactone were investigated for many years after it was approved for use in 1960.1 Gardiner et al. examined the metabolism of spironolactone 100 mg/day in 12 healthy males over the course of 15 days.2 Participants were 18 to 39 years of age with a median weight of 70 kg. Blood samples were taken on days 1, 8, and 15. Serum concentration of spironolactone and its metabolites increased from day one to eight but did not increase from day 8 to 15. These findings suggest steady state conditions occur by day eight. On day 15, the mean peak serum concentration of spironolactone, 80 ng/ml, occurred at 2.6 hours. The main metabolite of spironolactone, 7 α-thiomethylspironolactone (7 α-TMS), peaked at 391 ng/ml at 3.2 hours. The half-lives of spironolactone and 7 α-TMS were 1.4 and 13.8 hours respectively.
Spironolactone is metabolized by the liver. In patients with liver disease, spironolactone and its metabolites are present in higher peak serum concentrations and have longer half-lives with the same dose of spironolactone.3 For example, after administration of 100 mg spironolactone, levels of 7 α-TMS in patients with liver disease were 104.7 ng/ml at 2.3 hours and 532.1 ng/ml at 3.3 hours.
To determine the clinical effect of spironolactone on blood pressure, patients were followed for several weeks.4,5 In a study analyzing the effects of a high dose (400 mg daily) of spironolactone on blood pressure, significant reductions were found after one week of treatment.4 Patients (n=90) with hypertension (BP above 160/100 mm Hg at baseline) were given 100 mg of spironolactone every six hours, and blood pressure was recorded at one, two, and three weeks after the start of treatment. After three weeks of treatment, 49 of 90 patients achieved blood pressure <145/95 mm Hg.
In another study, patients with resistant hypertension and type 2 diabetes were followed for 16 weeks after randomization to receive either placebo or low dose (25 mg) of spironolactone.5 After four weeks of daily spironolactone treatment, blood pressure was measured and the dosage was adjusted to reach a goal blood pressure of 130/80 mm Hg. The spironolactone group saw an overall reduction of blood pressure over four to eight weeks. The maximum reduction of blood pressure (11.3/5.3 mm Hg, p<0.0001) occurred at eight weeks. There were no further reductions found at the 16 week follow-up. The findings of these studies suggest that the blood pressure reduction from spironolactone treatment can be observed after about four weeks, depending on the dosage.
- Aldactone [package insert]. New York, NY: Pfizer, Inc.; 2018.
- Gardiner P, Schrode K, Quinlan D, et al. Spironolactone metabolism: steady-state serum levels of the sulfur-containing metabolites. J Clin Pharmacol. Apr 1989;29(4):342-347.
- Sungaila I, Bartle WR, Walker SE, et al. Spironolactone pharmacokinetics and pharmacodynamics in patients with cirrhotic ascites. Gastroenterology.102(5):1680-1685.
- Crane MG, Harris JJ. Effect of spironolactone in hypertensive patients. Am J Med Sci. Dec 1970;260(6):311-330.
- Oxlund CS, Henriksen JE, Tarnow L, Schousboe K, Gram J, Jacobsen IA. Low dose spironolactone reduces blood pressure in patients with resistant hypertension and type 2 diabetes mellitus: a double blind randomized clinical trial. J Hypertens. Oct 2013;31(10):2094-2102.