CLINICAL RELEVANCE: DRUG–DRUG INTERACTION,PHARMACOKINETICS,PHARMACODYNAMICS, AND TOXICITY - Drug Transporters: Molecular Characterization and Role in Drug Disposition - page 798

TABLE 24.2. Examples of the Possible Involvement of Organic Anion and Cation
Transporters in Clinical Drug-Drug Interactions
Inhibitor/ Measured Putative

Drug Inducer Effect/Toxicity Mechanism Refs.

Penicillin Probenecid Decreased renal

clearance, prolonged
half-life

Inhibition of
OATs

720,721

ACE inhibitors Probenecid Decreased renal

clearance, prolonged
half-life

Inhibition of
OATs

721-726

Methotrexate Penicillin Decreased renal

clearance, increased
toxicity

Inhibition of
OATs

721,727-
730

NSAIDs Decreased renal

clearance

Inhibition of
OATs

529,557-
559,
563,564

Probenecid Decreased renal

clearance

Inhibition of
OATs

529,555,
730

Adefovir/
cidofovir

Probenecid Reduced

nephrotoxicity

Inhibition of
OATs

569,731-
733

Cephalosporins Probenecid Increased peak plasma

concentration and
terminal half-life

Inhibition of
OATs

565,734-
736

Furosemide Probenecid Decreased renal

clearance

Inhibition of
OATs

571

Zidovudine Cimetidine Decreased renal

clearance

Inhibition of
OCTs, OATs

737,738

Probenecid Decreased renal

clearance

Inhibition of
OATs

738-740

Famotidine Probenecid Increased plasma

concentration,
decreased renal
clearance

Inhibition of
OATs

575

Oxypurinol Benzbromarone Decreased plasma

level, increased renal
clearance

Inhibition of
URAT1

577,579

Digoxin Amiodarone Increased plasma levels

and toxicity

Inhibition of
OATPs, MDR1

276,649,
652,654,
741

Fexofenadine Fruit juices

(grapefruit,
orange,
apple)

Decreased plasma
AUC and maximum
plasma
concentration

Inhibition of
OATPs, MDR1

128,140

Erythromycin Increased plasma levels Inhibition of

OATPs, MDR1

123,742

Repaglinide Cyclosporin A Increased plasma AUC Inhibition of

OTAPs, MDR1

607,743,
744