Effect of genetic polymorphisms on the pharmacokinetics of gefitinib in healthy Chinese volunteers
Gefitinib is the first-generation drug of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) metabolised by the cytochrome P450 and transported by P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). In the present study, the pharmacokinetics of gefitinib in healthy Chinese volunteers was investigated and the effect of genetic polymorphisms on its variability was evaluted.Forty-five healthy volunteers were administered a single dose of gefitinib and the blood samples were used for quantifying the concentration of gefitinib and genotyping fifteen single-nucleotide polymorphisms of cytochrome P450 enzymes (CYP3A4, CYP3A5, CYP2D6, CYP2C9 and CYP2C19) and drug transporters (ABCB1 and ABCG2).CYP3A5*3 (rs776746) polymorphism showed a significant influence, with higher gefitinib AUC0-t in carrier of CC genotype than in CT/TT genotype (BH-adjusted p value <0.05). For CYP2C9*3 (rs1057910), significant differences in pharmacokinetics of gefitinib were detected between carriers of AA and AC genotypes, with higher AUC0-t, AUC0-∞ and Cmax in carrier of AC genotype than in AA gen-otype (BH-adjusted p value <0.05). No associations were found between SNPs in CYP3A4, CYP2D6, CYP2C19, ABCB1, ABCG2 and the pharmacokinetics of gefitinib.The SNPs in CYP3A5*3 (rs776746) and CYP2C9*3 (rs1057910) were found to be associated with altered gefitinib pharmacokinetics in healthy Chinese volunteers.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2024 |
---|---|
Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:54 |
---|---|
Enthalten in: |
Xenobiotica; the fate of foreign compounds in biological systems - 54(2024), 1 vom: 15. Jan., Seite 38-44 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Chen, Ying-Rong [VerfasserIn] |
---|
Links: |
---|
Anmerkungen: |
Date Completed 19.03.2024 Date Revised 19.03.2024 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1080/00498254.2023.2294039 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM365764493 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM365764493 | ||
003 | DE-627 | ||
005 | 20240319232400.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2024 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1080/00498254.2023.2294039 |2 doi | |
028 | 5 | 2 | |a pubmed24n1336.xml |
035 | |a (DE-627)NLM365764493 | ||
035 | |a (NLM)38085693 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Chen, Ying-Rong |e verfasserin |4 aut | |
245 | 1 | 0 | |a Effect of genetic polymorphisms on the pharmacokinetics of gefitinib in healthy Chinese volunteers |
264 | 1 | |c 2024 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 19.03.2024 | ||
500 | |a Date Revised 19.03.2024 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Gefitinib is the first-generation drug of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) metabolised by the cytochrome P450 and transported by P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). In the present study, the pharmacokinetics of gefitinib in healthy Chinese volunteers was investigated and the effect of genetic polymorphisms on its variability was evaluted.Forty-five healthy volunteers were administered a single dose of gefitinib and the blood samples were used for quantifying the concentration of gefitinib and genotyping fifteen single-nucleotide polymorphisms of cytochrome P450 enzymes (CYP3A4, CYP3A5, CYP2D6, CYP2C9 and CYP2C19) and drug transporters (ABCB1 and ABCG2).CYP3A5*3 (rs776746) polymorphism showed a significant influence, with higher gefitinib AUC0-t in carrier of CC genotype than in CT/TT genotype (BH-adjusted p value <0.05). For CYP2C9*3 (rs1057910), significant differences in pharmacokinetics of gefitinib were detected between carriers of AA and AC genotypes, with higher AUC0-t, AUC0-∞ and Cmax in carrier of AC genotype than in AA gen-otype (BH-adjusted p value <0.05). No associations were found between SNPs in CYP3A4, CYP2D6, CYP2C19, ABCB1, ABCG2 and the pharmacokinetics of gefitinib.The SNPs in CYP3A5*3 (rs776746) and CYP2C9*3 (rs1057910) were found to be associated with altered gefitinib pharmacokinetics in healthy Chinese volunteers | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a CYP2C9 | |
650 | 4 | |a CYP3A5 | |
650 | 4 | |a Gefitinib | |
650 | 4 | |a Genetic polymorphism | |
650 | 4 | |a Pharmacokinetics | |
650 | 7 | |a Cytochrome P-450 CYP3A |2 NLM | |
650 | 7 | |a EC 1.14.14.1 |2 NLM | |
650 | 7 | |a Gefitinib |2 NLM | |
650 | 7 | |a S65743JHBS |2 NLM | |
650 | 7 | |a ATP Binding Cassette Transporter, Subfamily G, Member 2 |2 NLM | |
650 | 7 | |a Cytochrome P-450 CYP2C19 |2 NLM | |
650 | 7 | |a EC 1.14.14.1 |2 NLM | |
650 | 7 | |a Cytochrome P-450 CYP2D6 |2 NLM | |
650 | 7 | |a EC 1.14.14.1 |2 NLM | |
650 | 7 | |a Cytochrome P-450 CYP2C9 |2 NLM | |
650 | 7 | |a EC 1.14.13.- |2 NLM | |
650 | 7 | |a Neoplasm Proteins |2 NLM | |
650 | 7 | |a Cytochrome P-450 Enzyme System |2 NLM | |
650 | 7 | |a 9035-51-2 |2 NLM | |
700 | 1 | |a Yu, Xiang |e verfasserin |4 aut | |
700 | 1 | |a Xu, Li-Min |e verfasserin |4 aut | |
700 | 1 | |a Mei, Jue |e verfasserin |4 aut | |
700 | 1 | |a Tian, Meng-Li |e verfasserin |4 aut | |
700 | 1 | |a Xu, Min |e verfasserin |4 aut | |
700 | 1 | |a Jin, Qiu-Yue |e verfasserin |4 aut | |
700 | 1 | |a Ye, Li-Bing |e verfasserin |4 aut | |
700 | 1 | |a Yang, Shui-Xin |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Xenobiotica; the fate of foreign compounds in biological systems |d 1971 |g 54(2024), 1 vom: 15. Jan., Seite 38-44 |w (DE-627)NLM000064742 |x 1366-5928 |7 nnns |
773 | 1 | 8 | |g volume:54 |g year:2024 |g number:1 |g day:15 |g month:01 |g pages:38-44 |
856 | 4 | 0 | |u http://dx.doi.org/10.1080/00498254.2023.2294039 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 54 |j 2024 |e 1 |b 15 |c 01 |h 38-44 |