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.
Suematsu
Fumihiro
F
Department of Hospital Pharmacy, Kyushu Kosei-Nenkin Hospital, 2-1-1 Kishinoura, Yahatanishi-Ku, Kitakyushu 806-8501, Japan. suematsu@ca.mbn.or.jp
Yukawa
Eiji
E
Yukawa
Miho
M
Minemoto
Masao
M
Ohdo
Shigehiro
S
Higuchi
Shun
S
Goto
Yoshinobu
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003404:Creatinine / Q000378:metabolism; D004077:Digoxin / Q000493:pharmacokinetics*; D004110:Diltiazem / Q000627:therapeutic use; D004347:Drug Interactions; D005260:Female; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008875:Middle Aged; D008954:Models, Biological; D015233:Models, Statistical; D009543:Nifedipine / Q000627:therapeutic use; D017891:Pharmacoepidemiology; D012044:Regression Analysis; D015203:Reproducibility of Results; D013148:Spironolactone / Q000627:therapeutic use; D014700:Verapamil / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D013148:Spironolactone; D004077:Digoxin; D003404:Creatinine; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine