Effects of omeprazole and AlOH/MgOH on riociguat absorption

Abstract

Introduction Riociguat, an oral soluble guanylate cyclase stimulator, is under investigation for pulmonary hypertension treatment. Aims Pharmacokinetic (PK) studies investigated the influence of omeprazole and AlOH/MgOH on riociguat absorption and bioavailability. Methods Oral, single-dose, immediate-release riociguat 2.5 mg was characterized in 2 open-label, randomized, crossover studies in healthy males: 1) 4-day omeprazole 40 mg od pre-treatment followed by co-treatment with omeprazole + riociguat vs riociguat alone on Day 5 (n=12); 2) co-treatment with 10 mL AlOH/MgOH + riociguat vs riociguat alone (n=12). Results Riociguat bioavailability was decreased slightly by pre- and co-treatment with omeprazole and co-treatment with 10 mL AlOH/MgOH (Table 1). This is considered of minor clinical relevance. The most common AEs in subjects treated with riociguat +/- omeprazole and AlOH/MgOH across the 2 studies were headache (44%) and abdominal pain upper (8%). No serious AEs were reported. Conclusions The results confirm the slightly reduced absorption of riociguat in neutral vs acidic medium. This is considered of minor clinical relevance. Riociguat +/- omeprazole or AlOH/MgOH was well tolerated with a good safety profile. Antacids should be taken at least 1 h after riociguat administration. (Table Presented).