Introduction: The ATP-binding cassette transporter ABCG2 can actively extrude a broad range of endogenous and exogenous substrates across biological membranes. Thereby, ABCG2 limits oral drug bioavailability, mediates hepatobiliary and renal excretion and participates functionally in the blood-brain barrier.
Areas covered: The paper provides a review of the clinical evidence of the role of ABCG2 in the bioavailability and brain disposition of drugs. It also sheds light on the value of experimental/preclinical data in predicting the role of ABCG2 in pharmacokinetics in humans.
Expert opinion: Experimental studies indicate that ABCG2 may limit the oral bioavailability and brain penetration of many drugs. ABCG2 has also been recognized as an important determinant of the disposition of some drugs in humans. For example, loss-of-function variants of ABCG2 affect the pharmacokinetics and pharmacodynamics of rosuvastatin in a clinically significant manner. Moreover, clinically relevant pharmacokinetic drug-drug interactions have been attributed to ABCG2 inhibition. However, examples from human studies are still rare compared with the overwhelming evidence from experimental studies. The large degree of functional redundancy of ABCG2 with other transporters such as P-glycoprotein may explain the rare occurrence of ABCG2-dependent drug-drug interactions in humans. Providing clinicians with consolidated information on the clinically relevant interactions of drugs with ABCG2 remains a matter of future exploration.