Drug Metabolism in Drug Design and Development Basic Concepts and Practice

Digoxin

Nifedipine



Increase in serum

concentration (+15%)

P-gp

Kleinbloesem et al. (1985)

Digoxin

Tiapamil



Increase in plasma

concentration(1.6-fold: 0.5–1.5

!

0.9–1.9 ng/mL)

P-gp

Lessem and Bellinetto (1983)

Digoxin

Spironolactone



Decrease in total

clearance (



31%) and

renal clearance(

18%)

P-gp

Fenster et al. (1984)

Digoxin

Itraconazole



Increase in AUC

(+68%), decreasein renal clearance(

20%)

P-gp

Jalava et al. (1997)

Digoxin

Clarithromycin



Decrease in

renal clearance(

48%)

P-gp

Wakasugi et al. (1998)

Digoxin

PSC-833(Valspodar)



Increase in AUC

(+76%), decreasein renal clearance(

62%)

P-gp

Kovarik et al. (1999)

Digoxin

Propafenone



Decrease in total

clearance (



31%),

decrease in renalclearance (



32%)

P-gp

Calvo et al. (1989)

Diltiazem

Grapefruit

juice



Increase in AUC

(+20%)

P-gp, CYP3A4

Christensen et al. (1989)

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)

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