PT - JOURNAL ARTICLE AU - Reiner Frey AU - Corina Becker AU - Sigrun Unger AU - Anja Schmidt AU - Georg Wensing AU - Wolfgang Mueck TI - Pharmacokinetics of the soluble guanylate cyclase stimulator riociguat in individuals with renal impairment DP - 2013 Sep 01 TA - European Respiratory Journal PG - P4073 VI - 42 IP - Suppl 57 4099 - http://erj.ersjournals.com/content/42/Suppl_57/P4073.short 4100 - http://erj.ersjournals.com/content/42/Suppl_57/P4073.full SO - Eur Respir J2013 Sep 01; 42 AB - Riociguat is the first oral soluble guanylate cyclase stimulator for the treatment of pulmonary hypertension. This pooled analysis of two non-randomized, non-blinded, observational studies evaluated the pharmacokinetics of riociguat and its metabolite M1 (BAY 60-4552) in individuals with and without renal impairment. Participants were assigned to 1 of 4 groups according to their creatinine clearance (CLCR): group 1, CLCR > 80 mL/min; group 2, CLCR 50–80 mL/min; group 3, CLCR 30–49 mL/min; group 4, CLCR < 30 mL/min. In the first study, group 4 received 0.5 mg riociguat; all other participants in both studies received 1 mg (single tablet doses). Pharmacokinetics were assessed using dense sampling. 63 participants (40 m, 23 f; age 36–78 years) completed the study. Riociguat was rapidly absorbed; median time to reach maximum concentration in plasma was 1 h in all 4 groups. Mean half-life of total riociguat was longer in groups 2–4 (9.5–11.4 h) than in group 1 (6.2 h), and renal clearance decreased with decreasing renal function. Exposure to total riociguat (mean area under the concentration–time curve/dose per kg body weight), was up to ∼100% higher in groups 2–4 than in group 1. However, exposure was highly variable in groups 2–4. Results for unbound riociguat and unbound M1 were similar to those for total riociguat and total M1. No serious or severe adverse events occurred. No change in safety or tolerability was observed with decreasing CLCR. Thus, the safety profile of riociguat in individuals with renal impairment was similar to that in healthy controls. Riociguat exposure was greater in individuals with renal impairment than in healthy controls, and was highly variable.