Abstract：
:Digoxin, which has a very narrow therapeutic window, is one of the most commonly prescribed drugs in the treatment of congestive heart failure. In some cases of atrial fibrillation digoxin is used in combination with verapamil. Verapamil can increase the plasma concentration of digoxin up to 60-90%. So far the precise mechanism of this pharmacokinetic drug-drug interaction is not known. Many studies suggest that verapamil reduces the renal clearance of digoxin. The energy-dependent membrane-bound transport enzyme, P-glycoprotein, may also be involved. Reports from oncology research show that verapamil can interact with P-glycoprotein as a modulator. Also taking into account that digoxin, like many anticancer drugs, is a substrate for P-glycoprotein, it is likely that P-glycoprotein modulation accounts for the digoxin-verapamil interaction. Current knowledge suggest that the non-competitive digoxin-verapamil interaction is due to inhibition of P-glycoprotein activity by verapamil resulting in a decreased renal tubular elimination of digoxin.
journal_name
Pharmacol Resjournal_title
Pharmacological researchauthors
Verschraagen M,Koks CH,Schellens JH,Beijnen JHdoi
10.1006/phrs.1999.0535keywords:
subject
Has Abstractpub_date
1999-10-01 00:00:00pages
301-6issue
4eissn
1043-6618issn
1096-1186pii
S1043-6618(99)90535-2journal_volume
40pub_type
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