Transportermediated Clinical Drugdrug Interactions

Transporter-mediated clinical drug-drug interaction occur but are less frequent than metabolic drug-drug interactions. Tables 4.5 and 4.6 summarize transporter-mediated clinical drug-drug interactions.

4.6 TRANSPORTER-MEDIATED CLINICAL DRUG-DRUG INTERACTIONS 71

Table 4.5. ABC transporter mediated clinical drug-drug interactions

Implicated transporter

Perpetrator - victim

Pharmacokinetic impact

P-gp

Quinidine - Digoxin

Digoxin renal CL decreases

34-48%

Ritonavir - Digoxin

Digoxin AUC increases 86%

Dronedarone -

Digoxin AUC increases 157%

Digoxin

Cmax increases 75%

Ranolazine -

Digoxin AUC increases 60%

Digoxin

Cmax increases 46%

BCRP

GF120918 -

Topotecan AUC increases

Topotecan

147%

Data from The International Transporter Consortium (2010)

Data from The International Transporter Consortium (2010)

Table 4.6. SLC transporter mediated clinical drug-drug interactions

Implicated

Perpetrator -

transporter

victim

Pharmacokinetic impact

OATPs

Cyclosporin -

Pravastatin AUC increases 890% and

Pravastatin

Cmax increase by 678%

Cyclosporin -

Rosuvastatin AUC increase 610%

Rosuvastatin

Cyclosporin -

Pitavastatin AUC increases 360%

Pitavastatin

Cmax increases 560%

Rifampicin -

Glyburide AUC increases 125%

Glyburide

Rifampicin -

Bosentan trough concentrations

Bosentan

increases 500%

Lopinavir /

Bosentan Day 4 trough concentration

ritonavir -

increase 4,700%. Day 10 trough

Bosentan

concentration increases 400%

Lopinavir/

Rosuvastatin AUC increases 107% and

ritonavir -

Cmax increases 365%

Rosuvastatin

OATs

Probenicid -

Cidofovir renal Cl decreases 32%

Cidofovir

Probenicid -

Furosemide renal Cl decreases 66%

Furosemide

Probenicid -

Acyclovir renal Cl decreases 32% and

Acyclovir

AUC increase 40%

OCTs

Cimetidine -

Metformin renal Cl decreases 27% and

Metformin

AUC increases 50%

Cimetidine -

Pindolol renal Cl decreases

Pindolol

approximately 34%

Continued

Continued

Table 4.6 Continued

Implicated Perpetrator -

transporter victim Pharmacokinetic impact

Table 4.6 Continued

Implicated Perpetrator -

transporter victim Pharmacokinetic impact

Cimetidine -

Varenicline AUC increases 29%

Varenicline

Cimetidine -

Dofetilide renal Cl decreases 33%

Dofetilide

Cimetidine -

Pilsicainide renal Cl decreases 28%

Pilsicainide

and AUC increases 33%

Cetirizine -

Pilsicainide renal Cl decreases 41%

Pilsicainide

Data from The International Transporter Consortium (2010)

Data from The International Transporter Consortium (2010)

With the exception of OATP-mediated drug-drug interactions, transporter-mediated drug-drug interactions are of a much less severe magnitude in comparison to metabolism-based drug-drug interactions.

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