Table S1.
Sampling procedures for PK and PD analysis and sample handling process
| Dose groups | Time points for blood sample collection | Time interval for urine sample collection | ||
|---|---|---|---|---|
| PK | SAD study | 10 mg, 25 mg 50 mg, 100 mg, 400 mg, 600 mg 200 mg (food interaction study) |
0 h (predose), 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h 0 h (predose), 0.5 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 3.5 h, 4 h, 5 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h (day 1) 0 h (predose), 0.5 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 3.5 h, 4 h, 5 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h (days 1 and 8) |
Day 1: 0–6 h, 6–12 h, 12–24 h Day 1: 0–6 h, 6–12 h, 12–24 h, 24–48 h, 48–72 h Day 1: 0–6 h, 6–12 h, 12–24 h Day 1: 0–6 h, 6–12 h, 12–24 h, 24–48 h, 48–72 h Day 8: 0–6 h, 6–12 h, 12–24 h, 24–48 h, 48–72 h |
| MAD study | 100 mg, 200 mg, 400 mg, 600 mg, 800 mg | Day 1: 0 h, 0.5 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 3.5 h, 4 h, 5 h, 6 h, 8 h, 12 h, 24 h Days 3–6: 0 h (predose) Day 7: 0 h, 0.5 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 3.5 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h 5 mL of blood was drawn and collected into a sodium heparinized tube. The blood samples were centrifuged at 1,500× g for 10 minutes at 4°C within 20 minutes after collection. After centrifugation, 1.5 mL of a plasma sample were added to 1.5 mL of 5% (v/v) formic acid in double distilled water and gently mixed. Two aliquots of 1 mL, 2 mL in total, were transferred into two Eppendorf tubes |
Day 1: 0–6 h, 6–12 h, 12–24 h Day 1: 0–6 h, 6–12 h, 12–24 h Day 7: 0–6 h, 6–12 h, 12–24 h, 24–48 h, 48–72 h 5 mL of a urine sample was added into tubes containing 5 mL of 5% (v/v) formic acid in double distilled water and was gently mixed. Two aliquots of 5 mL of urine each were transferred into polypropylene tubes |
|
| PD | SAD study | 10 mg, 25 mg, 50 mg, 100 mg, 400 mg, 600 mg 200 mg (food interaction study) |
Day 1: 0 h, 6 h, 12 h, 24 h (day 1, predose) Day 1: 6 h, 12 h, 24 h Day 1: 0 h, 6 h, 12 h, 24 h (day 1, predose) Day 1: 6 h, 12 h, 24 h Day 8: 0 h (predose), 6 h, 12 h, 24 h |
Day 1: 0–6 h, 6–12 h, 12–24 h Day 1: 0–6 h, 6–12 h, 12–24 h, 24–48 h, 48–72 h Day 1: 0–6 h, 6–12 h, 12–24 h Day 1: 0–6 h, 6–12 h, 12–24 h, 24–48 h, 48–72 h Day 8: 0–6 h, 6–12 h, 12–24 h, 24–48 h, 48–72 h |
| MAD study | 100 mg, 200 mg, 400 mg, 600 mg, 800 mg | Day 1: 0 h, 6 h, 12 h, 24 h (day 1, predose) Day 1: 6 h, 12 h, 24 h Days 3–6: 0 h (predose) Day 7: 0 h (predose), 6 h, 12 h, 24 h Within 20 minutes of the collection, it was centrifuged at 1,500× g, 4°C, and two aliquots of 1 mL of serum, 2 mL in total, were transferred into two Eppendorf tubes |
Day 1: 0–6 h, 6–12 h, 12–24 h Day 1: 0–6 h, 6–12 h, 12–24 h Day 7: 0–6 h, 6–12 h, 12–24 h, 24–48 h, 48–72 h Two aliquots of 5 mL of urine for the PD analysis were transferred into polypropylene tubes |
Note: All of the PK and PD aliquots were stored at −70°C until analysis.
Abbreviations: PK, pharmacokinetic; PD, pharmacodynamic; SAD, single ascending dose; h, hours; MAD, multiple ascending dose.