Effects of long-term oral carvedilol on the steady-state pharmacokinetics of oral digoxin in patients with mild to moderate hypertension.
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 (Cmax), mean time to maximum concentration (Tmax), concentration at 24 hours after the dose (C24), 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 Cmax for digoxin increased by 14% and 32%, respectively (p < 0.05), with no change in Tmax. 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.
Wermeling
D P
DP
Drug Product Evaluation Unit, College of Pharmacy, University of Kentucky, Lexington 40536-0082.
Field
C J
CJ
Smith
D A
DA
Chandler
M H
MH
Clifton
G D
GD
Boyle
D A
DA
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D002227:Carbazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000077261:Carvedilol; D004077:Digoxin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011412:Propanolamines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D013997:Time Factors
D000959:Antihypertensive Agents; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D004077:Digoxin