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Pharmacokinetics of felodipine and effect on digoxin plasma levels in patients with heart failure

, : Pharmacokinetics of felodipine and effect on digoxin plasma levels in patients with heart failure. Drugs 34 Suppl 3: 33-42

Some calcium antagonist drugs used in hypertension and cardiac diseases have been shown to increase plasma digoxin levels mainly as a result of reduced renal clearance. Felodipine is a new dihydropyridine calcium antagonist drug with cardiovascular effects, whose pharmacokinetics and effects on plasma digoxin levels have been studied in patients with left ventricular failure. 12 patients (11 men) on long term digoxin therapy were given 2.5 or 5 mg felodipine bid for 7 days followed by 1 week on 10mg bid. Plasma levels of digoxin and felodipine were measured before dosage and 30, 60 and 90 minutes and 2, 3, 4, 6, 8, 10 and 24 hours after the first dose and after 1 week of therapy (steady state). The area under plasma concentration versus time curve was calculated after the first dose and in steady state both for digoxin and felodipine. The absorption characteristics Cmax and Tmax were calculated both for felodipine and digoxin on the different felodipine doses. There was a linear relationship between dose and plasma level of felodipine. Plasma half-life in the 4- to 10-hour period of felodipine was 5.5 hours after a 10mg single dose, and 12 hours after 10mg bid. Felodipine 2.5mg, 5mg and 10mg all transiently increased peak plasma digoxin concentrations (by about 40%) at 1 hour after intake. Urinary excretion of digoxin during the day was unchanged, but impaired renal clearance may account for the transient increase in digoxin plasma level after felodipine.


PMID: 3443063

DOI: 10.2165/00003495-198700343-00009

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