Drug Metabolism in Drug Design and Development Basic Concepts and Practice

TABLE 6.3 (

Continued

)

Substrate

Inhibitor

Inducer

Result

Possible interacting protein

Reference

Fluvastatin

Cyclosporin A



Increase in AUC

(1.9-fold)

Goldberg and Roth (1996)

Glipizide



Rifampin Decrease in AUC

(

22%) and

Cmax

(+18%), Decreasein

t1/2

(

35%)

P-gp, CYP2C9

Niemi et al. (2001)

Glyburide



Rifampin Decrease in AUC

(

39%) and

Cmax

(

22%), Decrease

in

t1/2

(

17%)

P-gp, CYP2C9

Niemi et al. (2001)

Indinavir



St. John’s

wort

Decrease in AUC

(

57%) and

Cmax

(12.3

!

8.9), no

change in

t1/2

P-gp, CYP3A4

Piscitelli et al. (2000)

Irinotecan

(CPT11)

Huangqin



significant improvement

in diarrhea grades(P

= 0.044) as well

as a reduced frequencyof diarrheagrades 3 and 4

Multiple factors, one

of them could bedue to modulation

of P-gp

Mori et al. (2003)

Losartan

Grapefruit juice



Increase in

AUC (+17%)

P-gp, CYP3A4

Zaidenstein et al. (2001)

Loperamide

Quinidine(600 mg/m

2 )



Increase in AUC

(2.5-fold), expressionof respiratorydepression

P-pg

Sadeque et al. (2000b)

166