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Pharmacokinetics of the soluble guanylate cyclase stimulator riociguat in individuals with renal impairment
© Frey et al; licensee BioMed Central Ltd. 2013
- Published: 29 August 2013
- Pulmonary Hypertension
- Renal Impairment
- Severe Adverse Event
- Dose Titration
- Individual Dose
Riociguat is the first oral, soluble guanylate cyclase stimulator under review for the treatment of pulmonary hypertension (PH), a progressive, ultimately fatal disease [1–7]. This pooled analysis of two studies evaluated the pharmacokinetics of riociguat and its metabolite M1 (BAY 60-4552) in individuals with and without renal impairment. The safety and tolerability of riociguat were also assessed.
Two non-randomized, non-blinded, observational studies with group stratification were conducted in a single centre in Germany, following Good Clinical Practice and relevant industry guidelines [8, 9]. Participants were assigned to one of four renal function 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, individuals in group 4 received riociguat 0.5 mg; all other participants in both studies received riociguat 1 mg (single tablet doses). Pharmacokinetic parameters were assessed using dense sampling.
Pharmacokinetic parameters of riociguat in healthy participants and in individuals with mild, moderate or severe renal impairment
Group 1 (CRCL > 80 mL/min) n = 16
Group 2 (CRCL 50–80 mL/min) n = 15
Group 3 (CRCL 30–49 mL/min) n = 16
Group 4a (CRCL < 30 mL/min) n = 16
Exposure to riociguat was higher in individuals with renal impairment (CLCR 15–80 mL/min) than in controls; particular care should be exercised during individual dose titration in patients with renal impairment.
The studies were funded by Bayer Pharma AG, Wuppertal, Germany, and performed by Atef Halabi, Clinical Trial Director, CRS Clinical Research Services Kiel GmbH, Lornsenstrasse 7, 24105 Kiel, Germany.
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