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 (l/day)=(87.9+2.71C(cr))0.872(CCB)0.880(CHF)0.937(SPI)0.854(DFAC), where C(cr) 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.