Evaluation of the Effect of Food on the Pharmacokinetics of SHR6390, An Oral CDK4/6 Inhibitor, in Healthy Volunteers
Background and Introduction SHR6390 is a new developed highly effective and selective small-molecule oral CDK4/6 inhibitor. We aimed to evaluate the effect of food on the pharmacokinetics of SHR6390 tablets. Methods In an open-label two-way crossover study, 24 healthy Chinese volunteers were randomly divided into Group A and Group B, and 12 volunteers in each group received a single oral dose of a SHR6390 150-mg tablet under fasting and high-fat conditions. Blood samples were collected and determined for pharmacokinetic analyses. A liquid chromatography-tandem mass spectrometry method was developed and validated for determining the SHR6390 concentration. Results The time to maximum plasma concentration was not significantly affected by a high-fat diet. Compared with the fasting group, maximum plasma concentration, i.e., the area under the concentration–time curve ($ AUC_{0–t} $ and $ AUC_{0–∞} $) was altered significantly, as evidenced by an increase of 56.9%, 38.6%, and 37.5% respectively. We identified seven metabolites of SHR6390 from the plasma samples, and we found no sex differences in metabolic pathways. All treatment-emergent adverse events were Grade 1 or 2. Conclusions Food intake increased the maximum plasma concentration, $ AUC_{0–t} $, and $ AUC_{0–∞} $ significantly compared with the fasting condition. Meanwhile, single-dose SHR6390 for two treatment cycles is safe. SHR6390 was administered in a fasting status in the pivotal phase III study (NCT03927456) and chosen for the final drug label..
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
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| Enthalten in: |
Drugs in R & D - 22(2022), 2 vom: 30. Mai, Seite 175-182 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Yan-ping [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Anmerkungen: |
© The Author(s) 2022 |
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| doi: |
10.1007/s40268-022-00390-7 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
OLC207884148X |
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| 520 | |a Background and Introduction SHR6390 is a new developed highly effective and selective small-molecule oral CDK4/6 inhibitor. We aimed to evaluate the effect of food on the pharmacokinetics of SHR6390 tablets. Methods In an open-label two-way crossover study, 24 healthy Chinese volunteers were randomly divided into Group A and Group B, and 12 volunteers in each group received a single oral dose of a SHR6390 150-mg tablet under fasting and high-fat conditions. Blood samples were collected and determined for pharmacokinetic analyses. A liquid chromatography-tandem mass spectrometry method was developed and validated for determining the SHR6390 concentration. Results The time to maximum plasma concentration was not significantly affected by a high-fat diet. Compared with the fasting group, maximum plasma concentration, i.e., the area under the concentration–time curve ($ AUC_{0–t} $ and $ AUC_{0–∞} $) was altered significantly, as evidenced by an increase of 56.9%, 38.6%, and 37.5% respectively. We identified seven metabolites of SHR6390 from the plasma samples, and we found no sex differences in metabolic pathways. All treatment-emergent adverse events were Grade 1 or 2. Conclusions Food intake increased the maximum plasma concentration, $ AUC_{0–t} $, and $ AUC_{0–∞} $ significantly compared with the fasting condition. Meanwhile, single-dose SHR6390 for two treatment cycles is safe. SHR6390 was administered in a fasting status in the pivotal phase III study (NCT03927456) and chosen for the final drug label. | ||
| 700 | 1 | |a Hu, Ming-hui |4 aut | |
| 700 | 1 | |a Lin, Ping-ping |4 aut | |
| 700 | 1 | |a Li, Ting |4 aut | |
| 700 | 1 | |a Liu, Shu-qin |4 aut | |
| 700 | 1 | |a Wang, Yu-ya |4 aut | |
| 700 | 1 | |a Li, Shao-rong |4 aut | |
| 700 | 1 | |a Li, Xiang-kun |4 aut | |
| 700 | 1 | |a Wang, Chen-jing |4 aut | |
| 700 | 1 | |a Cao, Yu |0 (orcid)0000-0002-3980-8133 |4 aut | |
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