Drug Metabolism in Drug Design and Development Basic Concepts and Practice

Digoxin



St. John’s

wort

Decrease in AUC

(0.75-fold, Day 15) andC

max

(0.74-fold)

P-gp

Johne et al. (1999)

Digoxin

PSC-833(Valspodar)



Increase in AUC

(+76%), decreasein renal clearance(

62%)

P-gp

Kovarik et al. (1999)

Digoxin

Quinidine



Increase in

C

max

(2-fold), Decreasein renal clearance(

50%)

P-gp

Yu (1999)

Digoxin

Talinolol



Increase in AUC

(1.23-fold) andC

max

(1.45), no

change in renalclearance, nochange in

t1/2

P-gp

Westphal et al. (2000a)

Digoxin

Grapefruit

juice



Increase in AUC

(1.1-fold), nochange in

C

max

P-gp, CYP3A4

Becquemont et al. (2001)

Digoxin

Verapamil



Increase in

C

max

(1.44-fold), decreasein biliary clearance(

43%), no change

in renal clearance

P-gp

Hedman et al. (1991)

(continued

)

161