RESUMEN
AIM: To evaluate the effects of canrenone as add-on therapy in patients already treated with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARBs) and hydrochlorothiazide at the maximum dosage (25 mg/d). METHOD: In this randomized, open-label, controlled trial, we enrolled 175 Caucasian patients with essential hypertension not well controlled by concomitant ACE-I or ARBs and hydrochlorothiazide. At baseline, 87 patients (57 males and 30 females) were randomized to add canrenone 50 mg, and 88 (56 males and 32 females) patients to canrenone 100 mg, once a day, for 3 months. At baseline and after 3 months, we evaluated blood pressure (BP), pulse pressure (PP), heart rate (HR), fasting plasma glucose (FPG), homeostasis model assessment insulin (HOMA Index), lipid profile, electrolytes, uric acid, estimated glomerular filtration rate (eGFR), plasma urea, aldosterone, B-type natriuretic peptide (BNP), and galectin-3. RESULTS: Blood pressure decreased with both dosages of canrenone, with a better effect with canrenone 100 mg (-20.26 vs -23.68 mm Hg for SBP, and -10.58 vs -12.38 mm Hg for DBP), without a clinically relevant increase in potassium levels. We did not observe any differences regarding FPG or HOMA Index, nor of lipid profile, with the exception of triglycerides, which increased compared to baseline with canrenone 50 mg (+0.25 vs +0.34 mEq/L). Creatinine slightly increased with canrenone 100 mg (+0.02 vs +0.05 mg/dL), although no variations of eGFR were observed in neither groups. There was an increase in aldosterone levels with canrenone 50 mg. No changes in BNP or galectin-3 were recorded. CONCLUSION: Both canrenone dosages gave a decrease in blood pressure, with a better effect with the higher dose, with only a slight increase in potassium and creatinine levels, which were not clinically relevant. Clinical Trials Registration Eudract number: 2010-023606-13; ClinicalTrials.gov NCT02687178.
Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Antihipertensivos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Canrenona/administración & dosificación , Hidroclorotiazida/administración & dosificación , Hipertensión/tratamiento farmacológico , Antagonistas de Receptores de Mineralocorticoides/administración & dosificación , Inhibidores de los Simportadores del Cloruro de Sodio/administración & dosificación , Anciano , Bloqueadores del Receptor Tipo 1 de Angiotensina II/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antihipertensivos/efectos adversos , Biomarcadores/sangre , Canrenona/efectos adversos , Quimioterapia Combinada , Hipertensión Esencial , Femenino , Humanos , Hidroclorotiazida/efectos adversos , Hipertensión/sangre , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Italia , Masculino , Persona de Mediana Edad , Antagonistas de Receptores de Mineralocorticoides/efectos adversos , Inhibidores de los Simportadores del Cloruro de Sodio/efectos adversos , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Canrenona/efectos adversos , Dermatitis Alérgica por Contacto/etiología , Antagonistas de Receptores de Mineralocorticoides/efectos adversos , Administración Tópica , Adulto , Alopecia/tratamiento farmacológico , Dermatitis Alérgica por Contacto/diagnóstico , Femenino , Humanos , Antagonistas de Receptores de Mineralocorticoides/administración & dosificación , Pruebas del ParcheRESUMEN
Spironolactone, a diuretic antagonist of aldosterone has an unexplained side effect of amenorrhea which could be due to an angiogenesis inhibition. In this study we compared the effects of spironolactone, canrenone an active metabolite of spironolactone and eplerenone a more selective mineralocorticoid antagonist in rats implanted with a fibrin gel chamber. Perforated plexiglass chambers filled with rat fibrin, spironolactone (50 microM), canrenone (100 microM), eplerenone (500 microM), DMSO (0.05%) and control were implanted into the dorsal subcutaneous space of wistar rats. After 14 days of implantation, an invasion of the fibrin gel chamber by neovascularised buds had occurred through the holes. The number of vessels in the central field and in two or three peripheral fields covering the surface of the bud, were measured for each drug tested and compared to the control. In spironolactone treated chambers, the numbers of peripheral and central vessels were significantly reduced compared to control (p < 0.001). Canrenone, eplerenone and DMSO did not reduce the number of vessels (m +/- ESM, ANOVA followed by Newman-Keuls test). Spironolactone but not canrenone, nor eplerenone inhibited vessels formation in vivo. This antiangiogenic activity appeared to be not related to the antimineralocorticoid effect of spironolactone.
Asunto(s)
Amenorrea/inducido químicamente , Canrenona/efectos adversos , Canrenona/farmacología , Antagonistas de Receptores de Mineralocorticoides/efectos adversos , Antagonistas de Receptores de Mineralocorticoides/farmacología , Neovascularización Fisiológica/efectos de los fármacos , Espironolactona/análogos & derivados , Espironolactona/efectos adversos , Espironolactona/farmacología , Amenorrea/fisiopatología , Animales , Canrenona/administración & dosificación , Eplerenona , Femenino , Fibrina , Humanos , Hipertensión/tratamiento farmacológico , Antagonistas de Receptores de Mineralocorticoides/administración & dosificación , Ratas , Espironolactona/administración & dosificaciónRESUMEN
The effects of oral cholestyramine 4 gm 8 times daily and spironolactone 300 mg daily, given independently and in combination, on the elimination rate of digitoxin were studied in 6 healthy subjects pretreated with 0.1 or 0.15 mg oral digitoxin daily for 30 days before each intervention. The mean pretreatment digitoxin concentrations for the group ranged from 21 +/- 2.9 (SD) ng/ml to 28.5 +/- 6.9 ng/ml. The mean control digitoxin half-life (t 1/2) was reduced from 141.6 to 84.4 by treatment with cholestyramine alone. Treatment with spironolactone alone prolonged the mean digitoxin t 1/2 to 192.2 hr. The mean digitoxin t 1/2 after both active drugs was intermediate at 102.9 hr. Spironolactone did not fulfill the expectation from animal studies that it would enhance the clearance of digitoxin by cholestyramine. The prolongation of digitoxin elimination after spironolactone may contraindicate this drug in digitoxin intoxication.
Asunto(s)
Resina de Colestiramina/farmacología , Digitoxina/metabolismo , Espironolactona/farmacología , Canrenona/efectos adversos , Resina de Colestiramina/administración & dosificación , Digitoxina/sangre , Interacciones Farmacológicas , Humanos , Espironolactona/administración & dosificación , Factores de TiempoRESUMEN
A double-blind study of Phanurane and placebo was conducted on 61 patients with mild essential hypertension. Each patient received 2 gelules daily (2 X 50 mg of canrenone) during a 2 month period. Statistical analysis has shown that patients on Phanurane experienced a significant decrease in systolic and diastolic blood pressure compared with patients on placebo. Clinical tolerance of canrenone was excellent. Uric acid and triglyceride levels remained normal.
Asunto(s)
Canrenona/uso terapéutico , Hipertensión/tratamiento farmacológico , Pregnadienos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Canrenona/efectos adversos , Ensayos Clínicos como Asunto , Método Doble Ciego , Femenino , Humanos , Hipertensión/metabolismo , Masculino , Persona de Mediana EdadRESUMEN
Canrenone was administered in doses of 2 x 82 mg and 2 x 164 mg per day over a period of 10 days to diabetic patients without cardiovascular, liver or kidney involvement. Aldosterone excretion and plasma aldosterone increased only slightly during both regimes. There was a clear-cut increase in aldosterone excretion only after discontinuation of canrenone. Excretion of sodium, potassium and fluid was not significantly changed either during or after treatment. The lack of effect of canrenone on the kidney was in contrast to the significant decrease in serum sodium and increase in serum potassium, and the significant, dose-dependent rise in plasma renin activity following canrenone administration. The increased plasma renin activity persisted for some days after discontinuation of canrenone. It is suggested that canrenone primarily exerted its effect in the distal part of the large intestine where ionic movements are most affected by aldosterone. The disproportionately slight increase in plasma aldosterone concentration and aldosterone excretion, in spite of the greatly elevated plasma renin activity and serum potassium level, is considered to be due to a direct inhibitory effect of canrenone on aldosterone production in the adrenals.