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: |
E-Artikel |
---|
Erscheinungsjahr: |
2022 |
---|---|
Erschienen: |
2022 |
Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
---|---|
Enthalten in: |
Drugs in R & D - 22(2022), 2 vom: 30. Mai, Seite 175-182 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Liu, Yan-ping [VerfasserIn] |
---|
Links: |
Volltext [kostenfrei] |
---|
Anmerkungen: |
© The Author(s) 2022 |
---|
doi: |
10.1007/s40268-022-00390-7 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
OLC2130793282 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | OLC2130793282 | ||
003 | DE-627 | ||
005 | 20230506030151.0 | ||
007 | cr uuu---uuuuu | ||
008 | 230506s2022 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1007/s40268-022-00390-7 |2 doi | |
035 | |a (DE-627)OLC2130793282 | ||
035 | |a (DE-He213)s40268-022-00390-7-e | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
082 | 0 | 4 | |a 610 |q VZ |
084 | |a 15,3 |2 ssgn | ||
084 | |a PHARM |q DE-84 |2 fid | ||
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 |
264 | 1 | |c 2022 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a Computermedien |b c |2 rdamedia | ||
338 | |a Online-Ressource |b cr |2 rdacarrier | ||
500 | |a © The Author(s) 2022 | ||
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 | |
773 | 0 | 8 | |i Enthalten in |t Drugs in R & D |d Springer International Publishing, 1999 |g 22(2022), 2 vom: 30. Mai, Seite 175-182 |h Online-Ressource |w (DE-627)357171527 |w (DE-600)2094513-9 |w (DE-576)273885987 |x 1179-6901 |7 nnns |
773 | 1 | 8 | |g volume:22 |g year:2022 |g number:2 |g day:30 |g month:05 |g pages:175-182 |
856 | 4 | 0 | |u https://dx.doi.org/10.1007/s40268-022-00390-7 |z kostenfrei |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a SYSFLAG_A | ||
912 | |a GBV_OLC | ||
912 | |a FID-PHARM | ||
912 | |a SSG-OPC-PHA | ||
912 | |a GBV_ILN_20 | ||
912 | |a GBV_ILN_22 | ||
912 | |a GBV_ILN_23 | ||
912 | |a GBV_ILN_24 | ||
912 | |a GBV_ILN_31 | ||
912 | |a GBV_ILN_40 | ||
912 | |a GBV_ILN_60 | ||
912 | |a GBV_ILN_62 | ||
912 | |a GBV_ILN_63 | ||
912 | |a GBV_ILN_65 | ||
912 | |a GBV_ILN_69 | ||
912 | |a GBV_ILN_73 | ||
912 | |a GBV_ILN_74 | ||
912 | |a GBV_ILN_95 | ||
912 | |a GBV_ILN_105 | ||
912 | |a GBV_ILN_110 | ||
912 | |a GBV_ILN_151 | ||
912 | |a GBV_ILN_161 | ||
912 | |a GBV_ILN_170 | ||
912 | |a GBV_ILN_206 | ||
912 | |a GBV_ILN_213 | ||
912 | |a GBV_ILN_230 | ||
912 | |a GBV_ILN_285 | ||
912 | |a GBV_ILN_293 | ||
912 | |a GBV_ILN_602 | ||
912 | |a GBV_ILN_702 | ||
912 | |a GBV_ILN_2001 | ||
912 | |a GBV_ILN_2003 | ||
912 | |a GBV_ILN_2005 | ||
912 | |a GBV_ILN_2007 | ||
912 | |a GBV_ILN_2008 | ||
912 | |a GBV_ILN_2009 | ||
912 | |a GBV_ILN_2010 | ||
912 | |a GBV_ILN_2011 | ||
912 | |a GBV_ILN_2014 | ||
912 | |a GBV_ILN_2015 | ||
912 | |a GBV_ILN_2020 | ||
912 | |a GBV_ILN_2025 | ||
912 | |a GBV_ILN_2031 | ||
912 | |a GBV_ILN_2048 | ||
912 | |a GBV_ILN_2055 | ||
912 | |a GBV_ILN_2056 | ||
912 | |a GBV_ILN_2057 | ||
912 | |a GBV_ILN_2061 | ||
912 | |a GBV_ILN_2111 | ||
912 | |a GBV_ILN_2136 | ||
912 | |a GBV_ILN_2153 | ||
912 | |a GBV_ILN_2190 | ||
912 | |a GBV_ILN_4012 | ||
912 | |a GBV_ILN_4037 | ||
912 | |a GBV_ILN_4112 | ||
912 | |a GBV_ILN_4125 | ||
912 | |a GBV_ILN_4126 | ||
912 | |a GBV_ILN_4249 | ||
912 | |a GBV_ILN_4305 | ||
912 | |a GBV_ILN_4306 | ||
912 | |a GBV_ILN_4307 | ||
912 | |a GBV_ILN_4313 | ||
912 | |a GBV_ILN_4322 | ||
912 | |a GBV_ILN_4323 | ||
912 | |a GBV_ILN_4324 | ||
912 | |a GBV_ILN_4325 | ||
912 | |a GBV_ILN_4338 | ||
912 | |a GBV_ILN_4367 | ||
912 | |a GBV_ILN_4700 | ||
951 | |a AR | ||
952 | |d 22 |j 2022 |e 2 |b 30 |c 05 |h 175-182 |