Evaluation of the Effect of Food on the Pharmacokinetics of SHR6390, An Oral CDK4/6 Inhibitor, in Healthy Volunteers
© 2022. The Author(s)..
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 (AUC0-t and AUC0-∞) 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, AUC0-t, and AUC0-∞ 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: |
E-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. Juni, Seite 175-182 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Yan-Ping [VerfasserIn] |
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| Links: |
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| Themen: |
CDK4 protein, human |
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| Anmerkungen: |
Date Completed 08.06.2022 Date Revised 16.07.2022 published: Print-Electronic ClinicalTrials.gov: NCT03927456 Citation Status MEDLINE |
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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): |
NLM341579793 |
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| 100 | 1 | |a Liu, Yan-Ping |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Evaluation of the Effect of Food on the Pharmacokinetics of SHR6390, An Oral CDK4/6 Inhibitor, in Healthy Volunteers |
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| 500 | |a Date Revised 16.07.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT03927456 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s). | ||
| 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 (AUC0-t and AUC0-∞) 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 | ||
| 520 | |a CONCLUSIONS: Food intake increased the maximum plasma concentration, AUC0-t, and AUC0-∞ 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 7 | |a Protein Kinase Inhibitors |2 NLM | |
| 650 | 7 | |a Tablets |2 NLM | |
| 650 | 7 | |a CDK4 protein, human |2 NLM | |
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| 700 | 1 | |a Hu, Ming-Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Ping-Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Ting |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Shu-Qin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yu-Ya |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Shao-Rong |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xiang-Kun |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Chen-Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Yu |e verfasserin |4 aut | |
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