Drug Metabolism in Drug Design and Development Basic Concepts and Practice

TABLE 6.3 (

Continued

)

Substrate

Inhibitor

Inducer

Result

Possible interacting protein

Reference

Cyclosporin A

Erythromycin



Increase in AUC

(2.15-fold), increasein bioavailability (36%!

60%), decrease in total

clearance (



13%)

P-gp, CYP3A4

Gupta et al. (1989)

Cyclosporine

Vitamin E



Increase in AUC

(1.61-fold) andC

max

(1.37-fold),

no change in theratio of AUC ofmetabolites to thatof parent drugs

P-gp

Chang et al. (1996)

Dexamethasone Erythromycin



Increase in AUC

(1.24-fold)

P-gp

Kovarik et al. (1998)

Digoxin

Atorvastatin



Increase in AUC

(1.15-fold) and

C

max

(1.2-fold). No change inrenal clearance

P-gp

Boyd et al. (2000)

Digoxin



Rifampin Decrease in AUC

(

30%, po), decrease

in bioavailability(

30%), Increase in

P-gp expressionlevel in duodenum(3.5-fold), no changein

t1/2

, no change

in renal clearance

P-gp

Greiner et al. (1999b)

160