CLINICAL RELEVANCE: DRUG–DRUG INTERACTION,PHARMACOKINETICS,PHARMACODYNAMICS, AND TOXICITY - Drug Transporters: Molecular Characterization and Role in Drug Disposition - page 754

TABLE 24.1. Examples of the Possible Involvement of MDR1 in Clinical Drug-Drug
Interactions

Inhibitor/ Measured Putative

Drug Inducer Effect/Toxicity Mechanism Refs.

Digoxin Quinidine Increased plasma

levels, decreased
renal clearance

Inhibition of MDR1 71,72

Verapamil Increased plasma

levels, decreased
renal clearance

Inhibition of MDR1 74,89

Talinolol Increased plasma levels

and AUC, decreased
renal clearance

Inhibition of MDR1 77

Clarithromycin Increased plasma

levels, decreased
renal clearance

Inhibition of MDR1 78

Erithromycin Increased plasma

levels, decreased
renal clearance

Inhibition of MDR1 80,274

Itraconazole Increased plasma

levels, decreased
renal clearance

Inhibition of MDR1 79,275

Statins (e.g.,
atorvastatin)

Increased plasma
levels, decreased
renal clearance

Inhibition of MDR1 277

Ritonavir Increased plasma AUC

and terminal
half-life, toxicity
effects

Inhibition of MDR1 90,103

Paclitaxel Cyclosporin A Increased apparent

bioavailability

Inhibition of MDR1,
CYP3A

162

Elacridar Increased

bioavailability

Inhibition of MDR1,
CYP3A

278

Docetaxel Cyclosporin A Increased

bioavailability

Inhibition of MDR1,
CYP3A

163

Saquinavir Ritonavir Increased apparent oral

bioavailability

Inhibition of MDR1,
CYP3A

92,95

Tacrolimus Verapamil Increased plasma levels

and toxicity

Inhibition of MDR1,
CYP3A

107

Ketoconazole Increased apparent oral

bioavailability

Inhibition of MDR1,
CYP3A

279

Talinolol Verapamil Increased plasma

levels a

Inhibition of MDR1 114,115

Erythromycin Increased AUC Inhibition of MDR1 112

Cyclosporin A Erythromicin Increased plasma AUC

and peak plasma
concentrations

Inhibition of MDR1,
CYP3A

280,281