At plasma levels obtained with dosing at 10 mg once daily, macitentan has no relevant inhibitory or inducing effects on CYP enzymes, and is neither a substrate nor an inhibitor of the multi-drug resistance protein (P-gp, MDR-1). Macitentan and its active metabolite are neither substrates nor inhibitors of the organic anion transporting polypeptides (OATP1B1 and OATP1B3) and do not significantly interact with proteins involved in hepatic bile salt transport, i.e., the bile salt export pump (BSEP) and the sodium-dependent taurocholate co-transporting polypeptide (NTCP).