Drug Metabolism in Drug Design and Development Basic Concepts and Practice

Tacrolimus

Ketoconazole



Increase in AUC (two fold),

increase in bioavailability(14%–30%), nochange in totalclearance andhepatic availability

P-gp, CYP3A4

Floren et al. (1997)

Tacrolimus



Rifampin Increase in clearance

(+47%), decreasein bioavailability(

51%)

P-gp, CYP3A4

Hebert et al. (1999)

Talinolol

Erythromycin



Increase in AUC

(+52%)

P-gp

Schwarz et al. (2000)

Talinolol

Verapamil



Decrease in AUC

(

24%)

P-gp

Schwarz et al. (1999)

Talinolol

Verapamil



Decrease in the

secretion into smallintestine (decreaseof secretion rate: 29–59%)

P-gp

Gramatte and Oertel (1999)

Talinolol



Rifampin Decrease in AUC

(po:



21%; iv:



35%),

increase in P-gpexpression level(4.2-fold) induodenum

P-gp

Westphal et al. (2000d)

Taxol

(Paclitaxel)

Cyclosporin A



Increase in AUC

(8.5-fold), increasein total clearance(eight fold)

P-gp, CYP3A4

Meerum Terwogt et al. (1999)

Taxol

(Paclitaxel)

GF120918



Increase in AUC

P-gp

Malingre et al. (2001a)

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)

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