Contribution of Uptake and Efflux Transporters to Oral Pharmacokinetics of Furosemide
Revathi Chapa, Cindy Yanfei Li, Abdul Basit, Aarzoo Thakur, Mayur K. Ladumor, S.C. Sharma, Saranjit Singh, Arzu Selen, Bhagwat Prasad
Abstract
data and PBPK model suggest that the absorption of furosemide is permeability-limited, and OATP2B1 and MRP4 are important for its permeability across intestinal membrane. Further, as furosemide has been proposed as a probe substrate of renal organic anion transporters (OATs) for assessing clinical drug-drug interactions (DDIs) during drug development, the confounding effects of intestinal transporters identified in this study on furosemide PK should be considered in the clinical transporter DDI studies.
Topics & Concepts
Physiologically based pharmacokinetic modellingFurosemidePharmacologyPharmacokineticsMultidrug resistance-associated protein 2ChemistryEffluxBioavailabilityTransporterOrganic anion transporter 1In vivoP-glycoproteinMedicineATP-binding cassette transporterBiochemistryMultiple drug resistanceBiologyAntibioticsBiotechnologyGeneOrganic chemistryDrug Transport and Resistance MechanismsPharmacological Effects and Toxicity StudiesAntibiotics Pharmacokinetics and Efficacy