Drug Metabolism in Drug Design and Development Basic Concepts and Practice
manifold (two to eight fold) and seems to be related to MDR1 genotype (Lindell et al., 2003). The interindividual variation of P ...
TABLE 6.3 P-gp-mediated drug–drug interactions observed in clinic.Substrate Inhibitor Inducer Result Possible interacting protei ...
TABLE 6.3 ( Continued ) Substrate Inhibitor Inducer Result Possible interacting protein Reference Cyclosporin A Erythromycin ...
Digoxin St. John’s wort Decrease in AUC (0.75-fold, Day 15) andC max (0.74-fold) P-gp Johne et al. (1999) Digoxin PSC-833(Val ...
TABLE 6.3 ( Continued ) Substrate Inhibitor Inducer Result Possible interacting protein Reference Digoxin Quinine Increase in ...
Digoxin Nifedipine Increase in serum concentration (+15%) P-gp Kleinbloesem et al. (1985) Digoxin Tiapamil Increase in pla ...
TABLE 6.3 ( Continued ) Substrate Inhibitor Inducer Result Possible interacting protein Reference Docetaxel Cyclosporin A Inc ...
Etoposide PSC-833(Valspodar) Decrease in total clearance ( 41%), renal clearance ( 32%) and nonrenalclearance ( 48%) P- ...
TABLE 6.3 ( Continued ) Substrate Inhibitor Inducer Result Possible interacting protein Reference Fluvastatin Cyclosporin A I ...
Lovastatin Cyclosporin A Increase in AUC (5-fold) P-gp, CYP3A4 Kivisto et al. (1998) Lovastatin Diltiazem Increase in AUC ...
TABLE 6.3 ( Continued ) Substrate Inhibitor Inducer Result Possible interacting protein Reference Saquinavir Rifampin Decreas ...
Tacrolimus Ketoconazole Increase in AUC (two fold), increase in bioavailability(14%–30%), nochange in totalclearance andhepat ...
TABLE 6.3 (Continued ) Substrate Inhibitor Inducer Result Possible interacting protein Reference Taxol (Paclitaxel) Verapamil ...
6.5.1 Oral Absorption In humans, the role of transporters in drug absorption has been indirectly shown by inhibition or inductio ...
given dexamethasone’s wide therapeutic index and the short duration of coadministration (Kovarik et al., 1998). 6.5.2 Brain Pene ...
OAT-mediated secretion of methotrexate. By using mouse proximal tubule cells stably expressing human transporters, methotrexate ...
Grapefruit juice also diminished the AUC of fexofenadine variably among individuals. This decreased oral bioavailability is like ...
mL/min by inhibiting P-gp in the liver and kidney and inhibiting metabolizing enzymes. In a dose escalation study, patients rece ...
6.6 METHODS TO EVALUATE TRANSPORTER SUBSTRATE, INHIBITOR, OR INDUCER Given the important role of transporters in ADMET and drug- ...
throughput mode. However, the ATPase assay is not a functional transporter assay and can not distinguish substrates from inhibit ...
«
5
6
7
8
9
10
11
12
13
14
»
Free download pdf