Drug Metabolism in Drug Design and Development Basic Concepts and Practice

TABLE 6.3 P-gp-mediated drug–drug interactions observed in clinic.Substrate

Inhibitor

Inducer

Result

Possible interacting protein

Reference

Amitriptyline



St. John’s

wort

Decrease in

AUC (



22%)

P-gp, CYP3A4

Johne et al. (2002)

Amprenavir

Saquinavir



Increase in

AUC (+32%)

P-gp, CYP3A4

Sadler et al. (2001)

Atorvastatin

Erythromycin



Increase in AUC

(1.32-fold) andC

max

(1.38-fold).

No change in

t1/2

P-gp, CYP3A4

Siedlik et al. (1999)

Atorvastatin

Cyclosporin A



Increase in

AUC (7.4-fold)

P-gp, CYP3A4

Asberg et al. (2000)

Azithromycin

Nelfinavir



Increase in AUC

(2.06-fold) andC

max

(2.0-fold)

P-gp

Amsden et al. (2000)

Cerivastatin

Cyclosporin A



Increase in

AUC (3.8-fold)

OATPs

Muck et al. (1999)

Cyclosporin A

Grapefruit juice



Increase in

AUC (1.5-fold)

P-gp and CYP3A4

Edwards et al. (1999)

Cyclosporin A



St. John’s

wort

Decrease in whole-

blood troughconcentration(mean dose-normalized troughconcentration:0.84

!

0.48 ng/

(mL

mg))

P-gp, CYP3A4

Mai et al. (2000)

(continued

)

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