Additional file 1 of Results from in vitro and in vivo studies evaluating the bioavailability, effects of food, and administration as crushed tablet suspension on vericiguat pharmacokinetics
Creators: name: Becker, Corina
name: Boettcher, Michael
name: Muenster, Uwe
name: Loewen, Stephanie
name: Lobmeyer, Maximilian
name: Mueck, Wolfgang
Publisher: name: figshare
Year: 2022
Subjects: subject: Biochemistry
subject: Physiology
subject: FOS: Biological sciences
subject: Pharmacology
subject: Biotechnology
subject: 59999 Environmental Sciences not elsewhere classified
subject: FOS: Earth and related environmental sciences
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: 69999 Biological Sciences not elsewhere classified
subject: 19999 Mathematical Sciences not elsewhere classified
subject: FOS: Mathematics
subject: Science Policy
subject: 111714 Mental Health
subject: FOS: Health sciences

description: Additional file 1: Table S1. Vericiguat formulations administered within the clinical development program. Table S2. HPLC conditions for determination of vericiguat content in filtrate in dissolution studies. Table S3. Dissolution of vericiguat 10 mg as an intact tablet, crushed tablet suspension immediately after preparation, and as a crushed tablet suspension 4 h after preparation in 900 mL 0.01M HCl pH 2 at 37°C at 75 rpm. Table S4. Dissolution of vericiguat 10 mg as an intact tablet, crushed tablet suspension immediately after preparation, and as a crushed tablet suspension 4 h after preparation in 900 mL acetate buffer pH 4.5 at 37°C at 75 rpm. Table S5. Dissolution of vericiguat 10 mg as an intact tablet, crushed tablet suspension immediately after preparation, and as a crushed tablet suspension 4 h after preparation in 900 mL acetate buffer pH 6.8 at 37°C at 75 rpm. Figure S1. Mean (standard deviation) plasma concentrations of vericiguat (µg/L) after a single dose of vericiguat (intact tablet 10 mg) followed by a single 30-min intravenous infusion of 20 μg 14C-labeled vericiguat starting 4 h after oral vericiguat dosing (n = 10). Figure S2. Individual plasma concentrations of vericiguat (µg/L) after a single dose of vericiguat (intact tablet 10 mg) followed by a single 30-min intravenous infusion of 20 μg 14C-labeled vericiguat starting 4 h after oral vericiguat dosing (n = 10). Figure S3. Mean (standard deviation) plasma concentrations of vericiguat (µg/L) (dose normalized) after a single dose of vericiguat (intact tablet [fed and fasted] and PEG solution [fasted]), n = 15. Figure S4. Individual plasma concentrations of vericiguat (µg/L) after a single dose of vericiguat (n = 15) (A) 1.25 mg intact tablet fasted, (B) 5 mg intact tablet fasted, (C) 5 mg PEG solution fasted, (D) 5 mg intact tablet fed. Figure S5. Mean (standard deviation) plasma concentrations of vericiguat (µg/L) after a single dose of vericiguat (intact tablets [fed], n = 13). Figure S6. Individual plasma concentrations of vericiguat (µg/L) after a single dose of vericiguat (intact tablets [fed and fasted], n = 13). (A) 1.25 mg intact tablet fed, (B) 2.5 mg intact tablet fed, (C) 5 mg intact tablet fed, (D) 10 mg intact tablet fed. Figure S7. Mean (standard deviation) plasma concentrations of vericiguat (µg/L) after a single dose of vericiguat (intact tablet [fed and fasted], n = 29). Figure S8. Individual plasma concentrations of vericiguat (µg/L) after a single dose of vericiguat (A) 2.5 mg fed, (B) 5 mg fed, (C) 10 mg fed, (D) 10 mg fasted. Figure S9. Mean plasma concentrations of vericiguat (µg/L) after a single dose of vericiguat (intact tablet and crushed tablet, n = 29). Figure S10. Individual plasma concentrations of vericiguat (µg/L) after a single dose of vericiguat 10 mg (intact tablet and crushed tablet formulations, n = 29) (A) crushed tablet high-fat, high-calorie meal, (B) intact tablet high-fat, high-calorie meal, (C) intact tablet low-fat, low-calorie meal.