Effect of furosemide on plasma concentration and β-blockade by propranolol

Although propranolol and furosemide are used together for hypertension, the effects of furosemide on plasma levels and β-blocking action of propranolol are not known. Ten healthy subjects received propranolol 40 mg orally; the mean plasma propranolol levels in 60, 90, 180, and 300 min were 85 ± 16, 90 ± 7, 82 ± 8, and 58 ± 8 ng/ml. Propranolol was then given together with furosemide (25 mg orally) and the propranolol blood level was measured. Mean propranolol plasma levels were 106 ± 11 ng/ml at 60 min, 120 ± 12 ng/ml at 90 min (p <0.01), 102 ± 8 nglml at 180 min (p <0.05), and 78 ± 8 nglml at 300 min (p <0.01). Six additional subjects were given an infusion of 1 μg/min isoproterenol increased by 0.5 μg/min every 2 min until the heart rate rose by 25% after oral administration of furosemide 25 mg. This procedure was repeated after propranolol (40 mg orally) and propranolol with furosemide (25 mg orally). The amount of isoproterenol which raised the heart rate by 25% was 2.6 ± 0.3 μg after furosemide alone and 17.7 ± 2 μg after propranolol (p <0.01). After propranolol with furosemide the dose of isoproterenol required to elevate heart rate by 25% was 109 ± 15 μg (p <0.001).