Drug Metabolism in Drug Design and Development Basic Concepts and Practice

TABLE 6.3 (

Continued

)

Substrate

Inhibitor

Inducer

Result

Possible interacting protein

Reference

Saquinavir



Rifampin Decrease in AUC

(

70%)

P-gp, CYP3A4

Grub et al. (2001)

Saquinavir



Garlic Decrease AUC by 51%,

C

max

by 54% and

C

8h

by 49%

P-gp, CYP3A4 (?)

Piscitelli et al. (2002)

Simvastatin

Cyclosporin A



Increase in AUC

(2.6-fold)

P-gp, CYP3A4

Arnadottir et al. (1993)

Simvastatin

Diltiazem



Increase in AUC

(5-fold)

P-gp, CYP3A4

Mousa et al. (2000)

Simvastatin

Erythromycin



Increase in AUC

(6.2-fold) and

C

max

(3.4-fold)

P-gp, CYP3A4

Kantola et al. (1998)

Simvastatin Grapefruit juice



Increase in AUC

P-gp, CYP3A4,

OATP2?

Lilja et al. (1998)and Lilja et al. (2004)

Simvastatin

Itraconazole



Increase in AUC of

total simvastatin(18.6-fold)

P-gp, CYP3A4

Neuvonen et al. (1998)

Simvastatin

Verapamil



Increase in AUC

(4.6-fold) andC

max

(2.6-fold)

P-gp, CYP3A4

Kantola et al. (1998)

Sirolimus

Cyclosporine



Increase in AUC

(1.45-fold) andC

max

(1.71-fold)

P-gp, CYP3A4

Kaplan et al. (1998)

Tacrolimus

Diltiazem



Increase in blood

concentration(12.9–55 ng/mL)

P-gp, CYP3A4

Hebert and Lam (1999)

168