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The comparative effects of verapamil and a new dihydropyridine calcium channel blocker on digoxin pharmacokinetics
Author(s) -
Johnson Brian F,
Wilson John,
Marwaha Raj,
Hoch Kathleen,
Johnson Johanna
Publication year - 1987
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1987.109
Subject(s) - verapamil , isradipine , digoxin , dihydropyridine , pharmacokinetics , volume of distribution , volunteer , pharmacology , calcium channel blocker , medicine , calcium channel , drug interaction , diltiazem , urine , clinical pharmacology , calcium , heart failure , agronomy , biology
Conflicting conclusions have been reported about interaction of calcium channel blockers with digoxin. The effects of verapamil (240 mg/day) and a new dihydropyridine calcium channel blocker, isradipine (15 mg/day), on the pharmacokinetics of 1 mg intravenous digoxin were compared. All 24 volunteer subjects were healthy, male, nonobese, and aged 18 to 38 years. Groups of 12 subjects received each oral agent over 15 days, with collections of blood and urine for 72 hours after intravenous digoxin. Significant (P < 0.05) reduction in nonrenal (7.01 ± 1.97 to 4.00 ± 1.86 L/hr) and total clearance (14.1 ± 2.6 to 11.5 ± 2.5 L/hr) were induced by verapamil, without change in renal clearance. A near‐significant (P < 0.1) increase in peripheral volume of distribution contributed to prolonged elimination half‐life (23.1 ± 4.4 to 34.3 ± 9.7 hours). By contrast, isradipine caused only a 9% reduction in volume of distribution. Verapamil causes digoxin accumulation by reducing nonrenal elimination. No evidence of clinically relevant interaction of isradipine with digoxin was seen. Clinical Pharmacology and Therapeutics (1987) 42, 66–71; doi: 10.1038/clpt.1987.109