Macitentan is under development for the treatment of pulmonary arterial 
hypertension (PAH). Patients with PAH may suffer from comorbidities such as 
renal or hepatic impairment. Two prospective, single-center, open-label studies 
evaluated the pharmacokinetics of macitentan and its metabolites 
(pharmacologically active ACT-132577 and inactive ACT-373898) in healthy 
subjects and in subjects with mild, moderate, and severe hepatic impairment or 
severe renal function impairment (SRFI). After administering a single oral dose 
of 10 mg macitentan the pharmacokinetic parameters including area under the 
curve from zero to infinity (AUC∞) were derived from plasma concentration-time 
profiles. Exposure to macitentan and ACT-132577 was lower in hepatically 
impaired versus healthy subjects, with no correlation with the degree of hepatic 
impairment. Exposure to ACT-373898 was lower in subjects with moderate hepatic 
impairment only. Plasma concentration-time profiles for macitentan and 
ACT-132577 (active) were similar in healthy subjects and subjects with SRFI. 
AUC∞ of ACT-373898 (inactive) was 7.3-fold higher in subjects with SRFI versus 
healthy subjects. No safety concerns were raised in either study. Based on these 
observations, pharmacokinetic alterations of macitentan due to hepatic or renal 
function impairment are not considered clinically relevant and no dose 
adjustment is necessary in these patients.