Bioavailability, pharmacokinetics, and safety of riociguat given as an oral suspension or crushed tablet with and without food


Riociguat is approved for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Some patients have difficulty swallowing tablets; therefore, 2 randomized, nonblinded, crossover studies compared the relative bioavailability of riociguat oral suspensions and immediate-release (IR) tablet and of crushed-tablet preparations versus whole IR tablet. In study 1, 30 healthy subjects received 5 single riociguat doses: 0.3 and 2.4 mg (0.15 mg/mL suspensions), 0.15 mg (0.03 mg/mL), and 1.0 mg (whole IR tablet) under fasted conditions and 2.4 mg (0.15 mg/mL) after a high-fat, high-calorie American-style breakfast. In study 2, 25 healthy men received 4 single 2.5-mg doses: whole IR tablet and crushed IR tablet suspended in applesauce and water, respectively, under fasted conditions, and whole IR tablet after a continental breakfast. In study 1, dose-normalized pharmacokinetics of riociguat oral suspensions and 1.0-mg whole IR tablet were similar in fasted conditions; 90% confidence intervals for riociguat area under the curve (AUC) to dose and mean maximum concentration (Cmax) to dose were within bioequivalence criteria. After food, dose-normalized AUC and Cmaxdecreased by 15% and 38%, respectively. In study 2, riociguat exposure was similar for all preparations; AUC ratios for crushed-IR-tablet preparations to whole IR tablet were within bioequivalence criteria. The Cmax increased by 17% for crushed IR tablet in water versus whole IR tablet. Food intake decreased Cmax of the whole tablet by 16%, with unaltered AUC versus fasted conditions. Riociguat bioavailability was similar between the oral suspensions and the whole IR tablet; exposure was similar between whole IR tablet and crushed-IR-tablet preparations. Minor food effects were observed. Results suggest that riociguat formulations are interchangeable.

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Pharmacology: Pharmacokinetics and Pharmacodynamics
Pulmonary Arterial Hypertension
Pulmonary Hypertension


Soundos Saleh, Reiner Frey, Corina Becker, Sigrun Unger, Georg Wensing, Wolfgang Mück

Published in:

Pulmonary Circulation Vol 6: No S1 cover image

March 2016

Pulmonary Circulation Vol 6: No S1

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