Drug Metabolism in Drug Design and Development Basic Concepts and Practice

TABLE 6.3 (

Continued

)

Substrate

Inhibitor

Inducer

Result

Possible interacting protein

Reference

Digoxin

Quinine



Increase in

C

max

(1.1-fold), decreasein biliary clearance(

34%), no change in

renal clearance, nochange in plasmaconcentration

P-gp

Hedman et al. (1990)

Digoxin

Quinidine



Increase in

C

max

(1.54-fold), decreasein biliary clearance(

45%) and renal

clearance (



29%),

increase in plasmaconcentration(+55%)

P-gp

Hedman et al. (1990)

Digoxin

Amiodarone



Increase in plasma level

(C

max

: 1.55–2.85

m

g/L,

AUC: 7.2–12.1

m

g/L/h)

P-gp

Robinson et al. (1989)

Digoxin

Erythromycin



Increase in

C

max

(2.04-fold)

P-gp

Maxwell et al. (1989)

Digoxin

Propafenone



Decrease in total

clearance (



31%),

decrease in renalclearance (



32%)

P-gp

Calvo et al. (1989)

Digoxin

Diltiazem



The mean

trough increased1.38-fold.

P-gp

Andrejak et al. (1987)

162