Drug Metabolism in Drug Design and Development Basic Concepts and Practice

Lovastatin

Cyclosporin A



Increase in AUC

(5-fold)

P-gp, CYP3A4

Kivisto et al. (1998)

Lovastatin

Diltiazem



Increase in AUC

(3.6-fold)

P-gp, CYP3A4

Azie et al. (1998)

Lovastatin

Itraconazole



Increase in AUC

(more than 15-fold)

P-gp, CYP3A4

Kivisto et al. (1998)

Phenytoin

Kava



piperine increased Ka,

AUC(0–48), AUC(0-infinity), and delayedelimination of phenytoin.

P-gp, CYP3A4

Velpandian et al. (2001)

Quinacrine

Verapamil



Decrease in the

frequency of myoclonus(side effect)

P-gp

Satoh et al. (2004)

Quinidine

Itraconazole



Increase in AUC

(2.4-fold) and

C

max

(1.6-fold), decrease in renalclearance (



50%),

increase in

t1/2

(1.6-fold),

decrease in the ratioof AUC of metabolitesto that of parent drugs(

50%)

P-gp, CYP3A4

Kaukonen et al. (1997)

Saquinavir

Erythromycin



Increase in AUC

(1.99-fold)

P-gp, CYP3A4

Grub et al. (2001)

Saquinavir

Ketoconazole



Increase in AUC

(2.9-fold) and

C

max

(2.71-fold)

P-gp, CYP3A4

Grub et al. (2001)

Saquinavir

Ritonavir



Increase in AUC

(17-fold)

P-gp, CYP3A4

Buss et al. (2001)

(continued

)

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