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- Open Access
Absorption behavior of riociguat: bioavailability, food effects, and dose-proportionality
- Corina Becker†1Email author,
- Reiner Frey1,
- Christiane Hesse1,
- Sigrun Unger2,
- Michael Reber1 and
- Wolfgang Mueck1
© Becker et al; licensee BioMed Central Ltd. 2013
- Published: 29 August 2013
- Nitric Oxide
- Pulmonary Hypertension
- Pulmonary Arterial Hypertension
- Single Oral Dose
- Food Effect
Riociguat, an oral soluble guanylate cyclase (sGC) stimulator, is currently being investigated for the treatment of pulmonary hypertension. Riociguat has a novel dual mode of action, directly stimulating sGC, independent of nitric oxide (NO), and increasing sensitivity of sGC to NO. Riociguat thereby restores the NO–sGC–cGMP pathway, which is impaired in pulmonary hypertension. Three pharmacokinetic studies were performed to characterize the absorption behavior of riociguat including absolute bioavailability, food effects, and dose-proportionality.
The pharmacokinetic and safety profiles of riociguat were investigated in three open-label, randomized, crossover studies in healthy male subjects. In the absolute bioavailability study, fasted subjects (n=22) received a single oral immediate-release dose of riociguat 1 mg or intravenous riociguat 1 mg. In the food-effects study, subjects (n=23) received a single oral dose of immediate-release riociguat 2.5 mg after a 10-hour fast or after a high-fat high-calorie breakfast eaten within 30 minutes of dosing. In the dose-proportionality study, fasted subjects (n=24) received a single oral dose of riociguat 0.5, 1, 1.5, 2, or 2.5 mg.
Riociguat pharmacokinetics following a single oral dose of riociguat 2.5 mg in fed and fasted subjects (food-effects study)
Estimated fed:fasted ratio (%)
Riociguat shows complete oral absorption with no clinically relevant food effects; riociguat can therefore be taken with or without food. Riociguat systemic exposure increased dose proportionally over all doses (0.5–2.5 mg), supporting the suitability of the individualized dose-titration scheme used in the Phase III pulmonary arterial hypertension (PATENT) and chronic thromboembolic pulmonary hypertension (CHEST) studies.
The studies were funded by Bayer HealthCare Pharmaceuticals, Wuppertal, Germany. Medical writing assistance was provided by Adelphi Communications Ltd, Bollington, UK and funded by Bayer HealthCare Pharmaceuticals.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.