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Effects of Long‐Term Oral Carvedilol on the Steady‐State Pharmacokinetics of Oral Digoxin in Patients With Mild to Moderate Hypertension
Author(s) -
Wermeling Daniel P.,
Feild Carinda J.,
Smith Deborah A.,
Chandler Mary H.H.,
Clifton G. Dennis,
Boyle Duane A.
Publication year - 1994
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/j.1875-9114.1994.tb02857.x
Subject(s) - digoxin , pharmacokinetics , cmax , carvedilol , creatinine , medicine , renal function , oral administration , bioavailability , pharmacology , endocrinology , heart failure
The effect of multiple oral doses of carvedilol on steady‐state plasma digoxin pharmacokinetics was evaluated in 12 patients with mild to moderate hypertension. Area under the curve (AUC), mean maximum plasma concentration (C max ), mean time to maximum concentration (T max ), concentration at 24 hours after the dose (C 24 ), creatinine clearance, renal digoxin clearance, and urinary digoxin excretion were determined after patients took oral digoxin 0.25 mg once/day for 2 weeks. Carvedilol was added to the regimen, and digoxin pharmacokinetics were assessed after 2 weeks of concurrent treatment. The AUC and C max for digoxin increased by 14% and 32%, respectively (p<0.05), with no change in T max . The 24‐hour urinary digoxin excretion and 24‐hour renal digoxin clearance increased by 45% and 26%, respectively (p<0.05), with no change in creatinine clearance. Carvedilol appears to increase digoxin's oral bioavailability as well as renal elimination. The absolute change in digoxin pharmacokinetics was small and not clinically significant. The significance of the interaction in other patient populations remains to be studied.