Pharmacoepidemiologic detection of calcium channel blocker-induced change on digoxin clearance using multiple trough screen analysis

Nonlinear mixed effects modeling was used to estimate the effects of digoxin-calcium channel blockers (verapamil, diltiazem, nifedipine) in 336 serum levels gathered from 172 patients (104 male and 68 female) receiving oral digoxin as hospital in-patients. The final model describing digoxin clearance (CL) was CL (1/day) = (87.9+2.71C(cr))0.872(CCB)0.880(CHF)0.937(SPI)0.854(DFAC), where Cc, is the estimated creatinine clearance (ml/min); CCB=1 for concomitant administration of calcium channel blockers and CCB = zero otherwise; CHF = 1 for the patients with congestive heart failure and CHF = zero otherwise; SPI = 1 for concomitant administration of spironolactone and SPI = zero otherwise; DFAC = 1 for administration of a half-tablet of digoxin and DFAC = zero otherwise. Concomitant administration of calcium channel blockers; resulted in a 13% decrease in digoxin relative clearance. Copyright (C) 2002 John Wiley Sons, Ltd.