Inhibitors increase the AUC of substrate drugs by ≥1.25-fold.
Inducers decrease the AUC of substrate drugs by ≥1.20-fold.
• Sensitive substrates are when ≥25% of metabolism occurs via a given enzyme.
• Nonsensitive substrates are when <25% of metabolism occurs via a given enzyme.
Understanding the interaction of drugs with Pgp can assist with managing drug interactions. For example, adding carbamaze-pine (a Pgp inducer) to digoxin (a Pgp substrate) can lead to marked decreases in serum digoxin concentrations. Clinical management would include monitoring digoxin levels and making dose adjustments.
P-glycoprotein (Pgp) is a membrane-bound, active transport protein located in a number cells and tissues, including intestinal epithelial cells, various lymphocytes, biliary tract, brain, and proximal tubular cells of the kidney. ABCB1 is the name of the gene, while Pgp is the protein.
Its major function is as an efflux transporter of drugs and chemicals. Effects of inducers and inhibitors vary by their location. For example, Pgp transports substrate drugs out of the brain. Inducers may decrease concentrations in the CSF, because there is increased amount of Pgp available to transport substrates, while inhibitors may increase CSF concentrations.
Inhibitors. Abiraterone, amiodarone, atorvastatin, carvedilol, clarithromycin, cobicistat, crizotinib, cyclosporine, darunavir, dipyridamole, dronedarone, erythromycin, grapefruit juice, itraconazole, ivacaftor, ketoconazole, lapatinib, lomitapide, lopinavir, mefloquine, nelfinavir, nicardipine, nilotinib, progesterone, propranolol, quinidine, quinine, ranolazine, reserpine, ritonavir, saquinavir, sunitinib, tacrolimus, tamoxifen, telaprevir, ulipristal, vandetanib, vemurafenib, verapamil
Inducers. Carbamazepine, dexamethasone, doxorubicin, nefazodone, prazosin, rifampin, St. John’s wort, tenofovir, tipranavir, trazadone, vinblastine
Substrates (Sensitive). Aliskiren, amiodarone, atorvastatin, bosutinib, carfilzomib, carvedilol, cetirizine, cimetidine, ciprofloxacin, colchicine, crizotinib, cyclosporine, dabigatran, daunorubicin, desloratadine, dexamethasone, digitoxin, digoxin, diltiazem, docetaxel, doxorubicin, erythromycin, estradiol, etoposide, everolimus, fexofenadine, fosamprenavir, hydrocortisone, idarubicin, imatinib, indinavir, irinotecan, ivermectin, lapatinib, linagliptin, loperamide, loratadine, lovastatin, methotrexate, mitomycin, nadolol, nelfinavir, nicardipine, ondansetron, paclitaxel, paclitaxel protein bound, paliperidone, pazopanib, pomalidomide, pravastatin, quinidine, quinine, ranitidine, rnolazine, rifampin, risperidone, ritonavir, rivaroxaban, romidepsin, saquinavir, saxagliptin, silodosin, sirolimus, sitagliptin, tacrolimus, telaprevir, temsirolimus, teniposide, tolvaptan, trabectedin, vemurafenib, verapamil, vinblastine, vincristine, vismodegib