start-ver=1.4
cd-journal=joma
no-vol=49
cd-vols=
no-issue=8
article-no=
start-page=935
end-page=944
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2018
dt-pub=20181108
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Minor contribution of CYP3A5 to the metabolism of hepatitis C protease inhibitor paritaprevir in vitro
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= Paritaprevir (PTV) is a non-structural protein 3/4A protease inhibitor developed for the treatment of hepatitis C disease as a fixed dose combination of ombitasvir (OBV) and ritonavir (RTV) with or without dasabuvir. The aim of this study was to evaluate the effects of cytochrome P450 (CYP) 3A5 on in vitro PTV metabolism using human recombinant CYP3A4, CYP3A5 (rCYP3A4, rCYP3A5) and human liver microsomes (HLMs) genotyped as either CYP3A5*1/*1, CYP3A5*1/*3 or CYP3A5*3/*3. The intrinsic clearance (CLint, Vmax/Km) for the production of a metabolite from PTV in rCYP3A4 was 1.5 times higher than that in rCYP3A5. The PTV metabolism in CYP3A5*1/*1 and CYP3A5*1/*3 HLMs expressing CYP3A5 was comparable to that in CYP3A5*3/*3 HLMs, which lack CYP3A5. CYP3A4 expression level was significantly correlated with PTV disappearance rate and metabolite formation. In contrast, there was no such correlation found for CYP3A5 expression level. This study represents that the major CYP isoform involved in PTV metabolism is CYP3A4, with CYP3A5 having a minor role in PTV metabolism. The findings of the present study may provide foundational information on PTV metabolism, and may further support dosing practices in HCV-infected patients prescribed PTV-based therapy.
en-copyright=
kn-copyright=
en-aut-name=Su Nwe San
en-aut-sei=Su Nwe San
en-aut-mei=
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=MatsumotoJun
en-aut-sei=Matsumoto
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=SaitoYumi
en-aut-sei=Saito
en-aut-mei=Yumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=KoikeMasako
en-aut-sei=Koike
en-aut-mei=Masako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=SakaueHiroaki
en-aut-sei=Sakaue
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KatoYoshinori
en-aut-sei=Kato
en-aut-mei=Yoshinori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=FujiyoshiMasachika
en-aut-sei=Fujiyoshi
en-aut-mei=Masachika
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=AriyoshiNoritaka
en-aut-sei=Ariyoshi
en-aut-mei=Noritaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=YamadaHarumi
en-aut-sei=Yamada
en-aut-mei=Harumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
affil-num=1
en-affil=Graduate School of Pharmaceutical Sciences, International University of Health and Welfare
kn-affil=
affil-num=2
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama University
kn-affil=
affil-num=3
en-affil=Department of Pharmaceutical Sciences, School of Pharmacy , International University of Health and Welfare
kn-affil=
affil-num=4
en-affil=Department of Pharmaceutical Sciences, School of Pharmacy , International University of Health and Welfare
kn-affil=
affil-num=5
en-affil=Department of Biochemistry, School of Pharmacy , Tokyo University of Pharmacy and Life Sciences
kn-affil=
affil-num=6
en-affil=Department of Pharmaceutical Sciences, School of Pharmacy , International University of Health and Welfare
kn-affil=
affil-num=7
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama University
kn-affil=
affil-num=8
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama University
kn-affil=
affil-num=9
en-affil=Department of Pharmaceutical Sciences, School of Pharmacy , International University of Health and Welfare
kn-affil=
en-keyword=CYP3As
kn-keyword=CYP3As
en-keyword=DAA
kn-keyword=DAA
en-keyword=HCV
kn-keyword=HCV
en-keyword=LC-MS/MS
kn-keyword=LC-MS/MS
en-keyword=human liver microsomes
kn-keyword=human liver microsomes
en-keyword=metabolism
kn-keyword=metabolism
en-keyword=pharmacogenetics
kn-keyword=pharmacogenetics
END
start-ver=1.4
cd-journal=joma
no-vol=8
cd-vols=
no-issue=
article-no=
start-page=41
end-page=44
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20190731
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A proposed simple screening method to determine relative contributions of CYP3A4 and CYP3A5 to drug metabolism in vitro
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Purpose
The cytochrome P450 (CYP) 3A family of enzymes metabolize the majority of clinically used drugs. CYP3A4 and CYP3A5 are the two major CYP3A isoforms, but exhinbit different substrate specificity. The aim of this study was to establish a simple screening method to determine the relative contributions of CYP3A4 and CYP3A5 to drug metabolism in vitro.
Methods
A screening method was developed based on competitive inhibition using luciferin-PPXE (L-PPXE), a luminogenic CYP3A substrate. CYP3cide, tacrolimus, and midazolam were selected as standard compounds metabolized by CYP3A4 or CYP3A5. Nine clinically-used drugs were evaluated for their abilities to inhibit luminescence resulting from L-PPXE metabolism. Appropriate reaction conditions for the screening method were determined using recombinant CYP3A4 and CYP3A5.
Results
A significant decrease in luminescence resulting from L-PPXE metabolism by CYP3A4 and CYP3A5 was observed only for drugs reported to be metabolized by CYP3As. The substrate specificities of CYP3A4 or CYP3A5 for the proposed CYP3A substrates using our screening method were consistent with those of previous reports or available drug information from pharmaceutical companies. The reaction volume for this method was 50 μL, and the time required for the entire procedure was 70 min. Furthermore, this screening can be performed using a single tube with minimal training.
Conclusions
Through the establishment of our screening method in the present study, we are sure it is useful to determine the relative contributions of CYP3A4 and CYP3A5 to drug metabolism in vitro.
en-copyright=
kn-copyright=
en-aut-name=MatsumotoJun
en-aut-sei=Matsumoto
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=NakamuraHiroyoshi
en-aut-sei=Nakamura
en-aut-mei=Hiroyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=SanSu Nwe
en-aut-sei=San
en-aut-mei=Su Nwe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=SatoHikari
en-aut-sei=Sato
en-aut-mei=Hikari
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=TakezawaManami
en-aut-sei=Takezawa
en-aut-mei=Manami
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KishiRyuto
en-aut-sei=Kishi
en-aut-mei=Ryuto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=KitoYutaro
en-aut-sei=Kito
en-aut-mei=Yutaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=SuganoJunko
en-aut-sei=Sugano
en-aut-mei=Junko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=IzukiMai
en-aut-sei=Izuki
en-aut-mei=Mai
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=YanagisawaNao
en-aut-sei=Yanagisawa
en-aut-mei=Nao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=IkedaNaoki
en-aut-sei=Ikeda
en-aut-mei=Naoki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=SaitoYusuke
en-aut-sei=Saito
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=KatoYoshinori
en-aut-sei=Kato
en-aut-mei=Yoshinori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=YamadaHarumi
en-aut-sei=Yamada
en-aut-mei=Harumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=FujiyoshiMasachika
en-aut-sei=Fujiyoshi
en-aut-mei=Masachika
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=AriyoshiNoritaka
en-aut-sei=Ariyoshi
en-aut-mei=Noritaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
affil-num=1
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Pharmaceutical Sciences, International University of Health and Welfare
kn-affil=
affil-num=3
en-affil=Graduate School of Pharmaceutical Sciences, International University of Health and Welfare
kn-affil=
affil-num=4
en-affil=Department of Pharmaceutical Sciences, International University of Health and Welfare
kn-affil=
affil-num=5
en-affil=Department of Pharmaceutical Sciences, International University of Health and Welfare
kn-affil=
affil-num=6
en-affil=Department of Pharmaceutical Sciences, International University of Health and Welfare
kn-affil=
affil-num=7
en-affil=Department of Pharmaceutical Sciences, International University of Health and Welfare
kn-affil=
affil-num=8
en-affil=Department of Pharmaceutical Sciences, International University of Health and Welfare
kn-affil=
affil-num=9
en-affil=Department of Pharmaceutical Sciences, International University of Health and Welfare
kn-affil=
affil-num=10
en-affil=Department of Pharmaceutical Sciences, International University of Health and Welfare
kn-affil=
affil-num=11
en-affil=Department of Pharmaceutical Sciences, International University of Health and Welfare
kn-affil=
affil-num=12
en-affil=Department of Pharmaceutical Sciences, International University of Health and Welfare
kn-affil=
affil-num=13
en-affil=Department of Pharmaceutical Sciences, International University of Health and Welfare
kn-affil=
affil-num=14
en-affil=Department of Pharmaceutical Sciences, International University of Health and Welfare
kn-affil=
affil-num=15
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=16
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=CYP3A
kn-keyword=CYP3A
en-keyword=CYP3A5*3 allele
kn-keyword=CYP3A5*3 allele
en-keyword=P450 Glo Assay system
kn-keyword=P450 Glo Assay system
en-keyword=Pharmacokinetics
kn-keyword=Pharmacokinetics
en-keyword=Pharmacogenetics
kn-keyword=Pharmacogenetics
END
start-ver=1.4
cd-journal=joma
no-vol=65
cd-vols=
no-issue=
article-no=
start-page=143
end-page=153
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20191023
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Effect of CYP3A5*3 genetic variant on the metabolism of direct-acting antivirals in vitro : a different effect on asunaprevir versus daclatasvir and beclabuvir
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Direct-acting antivirals, asunaprevir (ASV), daclatasvir (DCV), and beclabuvir (BCV) are known to be mainly metabolized by CYP3A enzymes; however, the differences in the detailed metabolic activities of CYP3A4 and CYP3A5 on these drugs are not well clarified. The aim of the present study was to elucidate the relative contributions of CYP3A4 and CYP3A5 to the metabolism of ASV, DCV, and BCV, as well as the effect of CYP3A5*3 genetic variant in vitro. The amount of each drug and their major metabolites were determined using LC-MS/MS. Recombinant CYP3As and CYP3A5*3-genotyped human liver microsomes (CYP3A5 expressers or non-expressers) were used for the determination of their metabolic activities. The contribution of CYP3A5 to ASV metabolism was considerable compared to that of CYP3A4. Consistently, ASV metabolic activity in CYP3A5 expressers was higher than those in CYP3A5 non-expresser. Moreover, CYP3A5 expression level was significantly correlated with ASV metabolism. In contrast, these observations were not found in DCV and BCV metabolism. To our knowledge, this is the first study to directly demonstrate the effect of CYP3A5*3 genetic variants on the metabolism of ASV. The findings of the present study may provide basic information on ASV, DCV, and BCV metabolisms.
en-copyright=
kn-copyright=
en-aut-name=MatsumotoJun
en-aut-sei=Matsumoto
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=SanSu Nwe
en-aut-sei=San
en-aut-mei=Su Nwe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=FujiyoshiMasachika
en-aut-sei=Fujiyoshi
en-aut-mei=Masachika
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=KawauchiAyano
en-aut-sei=Kawauchi
en-aut-mei=Ayano
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=ChibaNatsumi
en-aut-sei=Chiba
en-aut-mei=Natsumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=TagaiRan
en-aut-sei=Tagai
en-aut-mei=Ran
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=SanbeRyoko
en-aut-sei=Sanbe
en-aut-mei=Ryoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=YanakaShiho
en-aut-sei=Yanaka
en-aut-mei=Shiho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=SakaueHiroaki
en-aut-sei=Sakaue
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=KatoYoshinori
en-aut-sei=Kato
en-aut-mei=Yoshinori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=NakamuraHiroyoshi
en-aut-sei=Nakamura
en-aut-mei=Hiroyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=YamadaHarumi
en-aut-sei=Yamada
en-aut-mei=Harumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=AriyoshiNoritaka
en-aut-sei=Ariyoshi
en-aut-mei=Noritaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
affil-num=1
en-affil=Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate
kn-affil=
affil-num=2
en-affil=Department of Pharmacokinetics, Pharmaceutical Sciences, International University of Health and Welfare
kn-affil=
affil-num=3
en-affil=Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate
kn-affil=
affil-num=4
en-affil=Department of Pharmacokinetics, Pharmaceutical Sciences, International University of Health and Welfare
kn-affil=
affil-num=5
en-affil=Department of Pharmacokinetics, Pharmaceutical Sciences, International University of Health and Welfare
kn-affil=
affil-num=6
en-affil=Department of Pharmacokinetics, Pharmaceutical Sciences, International University of Health and Welfare
kn-affil=
affil-num=7
en-affil=Department of Pharmacokinetics, Pharmaceutical Sciences, International University of Health and Welfare
kn-affil=
affil-num=8
en-affil=Department of Pharmacokinetics, Pharmaceutical Sciences, International University of Health and Welfare
kn-affil=
affil-num=9
en-affil=Department of Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
kn-affil=
affil-num=10
en-affil=Department of Pharmacokinetics, Pharmaceutical Sciences, International University of Health and Welfare
kn-affil=
affil-num=11
en-affil=Department of Pharmacokinetics, Pharmaceutical Sciences, International University of Health and Welfare
kn-affil=
affil-num=12
en-affil=Department of Pharmacokinetics, Pharmaceutical Sciences, International University of Health and Welfare
kn-affil=
affil-num=13
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama University
kn-affil=
en-keyword=Genetic markers
kn-keyword=Genetic markers
en-keyword=Haplotypes
kn-keyword=Haplotypes
END
start-ver=1.4
cd-journal=joma
no-vol=40
cd-vols=
no-issue=
article-no=
start-page=100407
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20211031
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Blood concentrations of tacrolimus upon conversion from rabeprazole to vonoprazan in renal transplant recipients: Correlation with cytochrome P450 gene polymorphisms
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=We evaluated the impact of vonoprazan on blood concentrations of tacrolimus via a retrospective analysis of 52 renal transplant recipients who took tacrolimus and converted from rabeprazole to vonoprazan between August 2018 and September 2019. We compared tacrolimus trough levels upon conversion among groups that were classified based on cytochrome P450 (CYP) gene polymorphisms. CYP3A5 groups were heterozygous or homozygous for CYP3A5∗1 and CYP3A5∗3 alleles. CYP2C19 genotypes were classified as extensive (∗1/∗1), intermediate (∗1/∗2 and ∗1/∗3) or poor metabolizers (∗2/∗2, ∗2/∗3 and ∗3/∗3). Tacrolimus trough levels increased only 0.3 ng/mL upon conversion in the CYP3A5∗3/∗3 group: 5.8 [3.4-7.2] vs 6.1 [3.8-7.9]; p = 0.06. No statistically significance changes in tacrolimus levels also occurred in the CYP3A5∗1/∗1 or CYP3A5∗1/∗3 groups. Subgroup analyses of CYP3A5∗3/∗3 demonstrated low changes for all three CYP2C19 subgroups: 5.2 [4.3-6.5] vs 6.2 [4.3-7.9]; p = 0.07, 6.1 [3.4-7.2] vs 6.7 [4.6-7.9]; p = 0.12 and 5.4 [3.6-6.5] vs 4.7 [3.8-6.3]; p = 1.00, respectively. Conversion to vonoprazan thus resulted in little increase of tacrolimus trough levels, even in the group predicted to be most susceptible (CYP3A5∗3/∗3 and 2C19∗1/∗1), thus supporting the safety of concomitant use of vonoprazan with tacrolimus.
en-copyright=
kn-copyright=
en-aut-name=WatariShogo
en-aut-sei=Watari
en-aut-mei=Shogo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=ArakiMotoo
en-aut-sei=Araki
en-aut-mei=Motoo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=MatsumotoJun
en-aut-sei=Matsumoto
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=YoshinagaKasumi
en-aut-sei=Yoshinaga
en-aut-mei=Kasumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=SekitoTakanori
en-aut-sei=Sekito
en-aut-mei=Takanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=MaruyamaYuki
en-aut-sei=Maruyama
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=MitsuiYosuke
en-aut-sei=Mitsui
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=SadahiraTakuya
en-aut-sei=Sadahira
en-aut-mei=Takuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=KubotaRisa
en-aut-sei=Kubota
en-aut-mei=Risa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=NishimuraShingo
en-aut-sei=Nishimura
en-aut-mei=Shingo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=WadaKoichiro
en-aut-sei=Wada
en-aut-mei=Koichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=KobayashiYasuyuki
en-aut-sei=Kobayashi
en-aut-mei=Yasuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=TakeuchiHidemi
en-aut-sei=Takeuchi
en-aut-mei=Hidemi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=TanabeKatsuyuki
en-aut-sei=Tanabe
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=KitagawaMasashi
en-aut-sei=Kitagawa
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=MorinagaHiroshi
en-aut-sei=Morinaga
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=KitamuraShinji
en-aut-sei=Kitamura
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=SugiyamaHitoshi
en-aut-sei=Sugiyama
en-aut-mei=Hitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=AriyoshiNoritaka
en-aut-sei=Ariyoshi
en-aut-mei=Noritaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=
en-aut-name=WatanabeMasami
en-aut-sei=Watanabe
en-aut-mei=Masami
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=
en-aut-name=WatanabeToyohiko
en-aut-sei=Watanabe
en-aut-mei=Toyohiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=
en-aut-name=NasuYasutomo
en-aut-sei=Nasu
en-aut-mei=Yasutomo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=23
ORCID=
affil-num=1
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=3
en-affil=Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=4
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=5
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=6
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=7
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=8
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=9
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=10
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=11
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=12
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=13
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=
affil-num=14
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=
affil-num=15
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=
affil-num=16
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=
affil-num=17
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=
affil-num=18
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=
affil-num=19
en-affil=Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=20
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=
affil-num=21
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=
affil-num=22
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=23
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Cytochrome P450
kn-keyword=Cytochrome P450
en-keyword= tacrolimus
kn-keyword= tacrolimus
en-keyword=renal transplantation
kn-keyword=renal transplantation
en-keyword=CYP2C19
kn-keyword=CYP2C19
en-keyword=vonoprazan
kn-keyword=vonoprazan
en-keyword=rabeprazole
kn-keyword=rabeprazole
END
start-ver=1.4
cd-journal=joma
no-vol=41
cd-vols=
no-issue=5
article-no=
start-page=2511
end-page=2521
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20215
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Relevance of CYP3A5 Expression on the Clinical Outcome of Patients With Renal Cell Carcinoma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background/Aim: This study aimed to elucidate the detailed characteristics of CYP3A5 expression and the association between CYP3A5 expression and clinical outcomes in patients with renal cell carcinoma (RCC). Patients and Methods: This study retrospectively enrolled 124 Japanese patients with RCC treated at the Okayama University Hospital. The commonest CYP3A5 gene polymorphism, CYP3A5*3, and expression levels of CYP3A5 mRNA and protein in each tissue were examined. Results: Expression of CYP3A5 mRNA and protein in RCC tissues was significantly down-regulated compared to that in adjacent normal tissues. High level of CYP3A5 mRNA expression significantly extended cancer-specific survival (p=0.004) and overall survival (p=0.002). The CYP3A5 mRNA expression level was identified as a significant independent prognostic factor for both cancer-specific survival and overall survival. Conclusion: CYP3A5 could serve as a potential marker for prognostication and treatment planning for patients with RCC.
en-copyright=
kn-copyright=
en-aut-name=MatsumotoJun
en-aut-sei=Matsumoto
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=KoteraYumi
en-aut-sei=Kotera
en-aut-mei=Yumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=WatariShogo
en-aut-sei=Watari
en-aut-mei=Shogo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=TakeuchiKoichi
en-aut-sei=Takeuchi
en-aut-mei=Koichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=UekiHideo
en-aut-sei=Ueki
en-aut-mei=Hideo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KoyamaToshihiro
en-aut-sei=Koyama
en-aut-mei=Toshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=WadaKoichiro
en-aut-sei=Wada
en-aut-mei=Koichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=FujiyoshiMasachika
en-aut-sei=Fujiyoshi
en-aut-mei=Masachika
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=NasuYasutomo
en-aut-sei=Nasu
en-aut-mei=Yasutomo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=AriyoshiNoritaka
en-aut-sei=Ariyoshi
en-aut-mei=Noritaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
affil-num=1
en-affil=Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=3
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=4
en-affil=Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=5
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=6
en-affil=Department of Pharmaceuticals Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=7
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=8
en-affil=Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=9
en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=10
en-affil=Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=human
kn-keyword=human
en-keyword=cytochrome P450 CYP3A
kn-keyword=cytochrome P450 CYP3A
en-keyword=renal cell carcinoma treatment outcome
kn-keyword=renal cell carcinoma treatment outcome
END
start-ver=1.4
cd-journal=joma
no-vol=478
cd-vols=
no-issue=8
article-no=
start-page=1779
end-page=1790
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20221226
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Significance of UGT1A6, UGT1A9, and UGT2B7 genetic variants and their mRNA expression in the clinical outcome of renal cell carcinoma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=UDP-glucuronosyltransferase (UGT) metabolizes a number of endogenous and exogenous substrates. Renal cells express high amounts of UGT; however, the significance of UGT in patients with renal cell carcinoma (RCC) remains unknown. In this study, we profile the mRNA expression of UGT subtypes (UGT1A6, UGT1A9, and UGT2B7) and their genetic variants in the kidney tissue of 125 Japanese patients with RCC (Okayama University Hospital, Japan). In addition, we elucidate the association between the UGT variants and UGT mRNA expression levels and clinical outcomes in these patients. The three representative genetic variants, namely, UGT1A6 541A > G, UGT1A9 i399C > T, and UGT2B7-161C > T, were genotyped, and their mRNA expression levels in each tissue were determined. We found that the mRNA expression of the three UGTs (UGT1A6, UGT1A9, and UGT2B7) are significantly downregulated in RCC tissues. Moreover, in patients with RCC, the UGT2B7-161C > T variant and high UGT2B7 mRNA expression are significantly correlated with preferable cancer-specific survival (CSS) and overall survival (OS), respectively. As such, the UGT2B7-161C > T variant and UGT2B7 mRNA expression level were identified as significant independent prognostic factors of CSS and CSS/OS, respectively. Taken together, these findings indicate that UGT2B7 has a role in RCC progression and may, therefore, represent a potential prognostic biomarker for patients with RCC.
en-copyright=
kn-copyright=
en-aut-name=MatsumotoJun
en-aut-sei=Matsumoto
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=NishimotoAnzu
en-aut-sei=Nishimoto
en-aut-mei=Anzu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=WatariShogo
en-aut-sei=Watari
en-aut-mei=Shogo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=UekiHideo
en-aut-sei=Ueki
en-aut-mei=Hideo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=ShiromizuShoya
en-aut-sei=Shiromizu
en-aut-mei=Shoya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=IwataNaohiro
en-aut-sei=Iwata
en-aut-mei=Naohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=TakedaTatsuaki
en-aut-sei=Takeda
en-aut-mei=Tatsuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=UshioSoichiro
en-aut-sei=Ushio
en-aut-mei=Soichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=KajizonoMakoto
en-aut-sei=Kajizono
en-aut-mei=Makoto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=FujiyoshiMasachika
en-aut-sei=Fujiyoshi
en-aut-mei=Masachika
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=KoyamaToshihiro
en-aut-sei=Koyama
en-aut-mei=Toshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=ArakiMotoo
en-aut-sei=Araki
en-aut-mei=Motoo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=WadaKoichiro
en-aut-sei=Wada
en-aut-mei=Koichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=ZamamiYoshito
en-aut-sei=Zamami
en-aut-mei=Yoshito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=NasuYasutomo
en-aut-sei=Nasu
en-aut-mei=Yasutomo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=AriyoshiNoritaka
en-aut-sei=Ariyoshi
en-aut-mei=Noritaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
affil-num=1
en-affil=Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=3
en-affil=Department of Urology, National Hospital Organization Okayama Medical Center
kn-affil=
affil-num=4
en-affil=Department of Urology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=5
en-affil=Department of Pharmacy, Okayama University Hospital
kn-affil=
affil-num=6
en-affil=Department of Pharmacy, Okayama University Hospital
kn-affil=
affil-num=7
en-affil=Department of Pharmacy, Okayama University Hospital
kn-affil=
affil-num=8
en-affil=Department of Pharmacy, Okayama University Hospital
kn-affil=
affil-num=9
en-affil=Department of Pharmacy, Okayama University Hospital
kn-affil=
affil-num=10
en-affil=Department of Pharmacy, Tottori University Hospital
kn-affil=
affil-num=11
en-affil=Department of Pharmaceuticals Biomedicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=12
en-affil=Department of Urology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=13
en-affil=Department of Urology, Faculty of Medicine, Shimane University
kn-affil=
affil-num=14
en-affil=Department of Pharmacy, Okayama University Hospital
kn-affil=
affil-num=15
en-affil=Department of Urology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=16
en-affil=Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Genetic variant
kn-keyword=Genetic variant
en-keyword=Polymorphism
kn-keyword=Polymorphism
en-keyword=Renal cell carcinoma
kn-keyword=Renal cell carcinoma
en-keyword=Survival
kn-keyword=Survival
en-keyword=UDP-glucuronosyltransferase
kn-keyword=UDP-glucuronosyltransferase
END
start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240119
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A comparison between the adverse event profiles of patients receiving palbociclib and abemaciclib: analysis of two real-world databases
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background Palbociclib and abemaciclib are cyclin-dependent kinase (CDK) 4/6 inhibitors currently used to treat breast cancer. Although their therapeutic efficacies are considered comparable, differences in adverse event (AE) profiles of the two drugs remain unclear.
Aim We analysed two real-world databases, the World Health Organization’s VigiBase and the Food and Drug Administration Adverse Event Reporting System (FAERS), to identify differences in AE profiles of palbociclib and abemaciclib.
Method Data of patients with breast cancer receiving palbociclib or abemaciclib recorded until December 2022 were extracted from the VigiBase and FAERS databases. In total, 200 types of AEs were analysed. The reporting odds ratios were calculated using a disproportionality analysis.
Results Cytopenia was frequently reported in patients receiving palbociclib, whereas interstitial lung disease and diarrhoea were frequently reported in those receiving abemaciclib. Moreover, psychiatric and nervous system disorders were more common in the palbociclib group, whereas renal and urinary disorders were more common in the abemaciclib group.
Conclusion This study is the first to show comprehensively the disparities in the AE profiles of palbociclib and abemaciclib. The findings highlight the importance of considering these differences when selecting a suitable CDK4/6 inhibitor to ensure safe and favourable outcomes for patients with breast cancer.
en-copyright=
kn-copyright=
en-aut-name=TakedaTatsuaki
en-aut-sei=Takeda
en-aut-mei=Tatsuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=SugimotoShiho
en-aut-sei=Sugimoto
en-aut-mei=Shiho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=MatsumotoJun
en-aut-sei=Matsumoto
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=IwataNaohiro
en-aut-sei=Iwata
en-aut-mei=Naohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=NakamotoAkihiko
en-aut-sei=Nakamoto
en-aut-mei=Akihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=OzakiAya Fukuma
en-aut-sei=Ozaki
en-aut-mei=Aya Fukuma
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=HamanoHirofumi
en-aut-sei=Hamano
en-aut-mei=Hirofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=AriyoshiNoritaka
en-aut-sei=Ariyoshi
en-aut-mei=Noritaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=ZamamiYoshito
en-aut-sei=Zamami
en-aut-mei=Yoshito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
affil-num=1
en-affil=Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Personalized Medicine and Preventive Healthcare Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=3
en-affil=Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=4
en-affil=Department of Pharmacy, Okayama University Hospital
kn-affil=
affil-num=5
en-affil=Department of Pharmacy, Okayama University Hospital
kn-affil=
affil-num=6
en-affil=Department of Clinical Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University of California
kn-affil=
affil-num=7
en-affil=Department of Pharmacy, Okayama University Hospital
kn-affil=
affil-num=8
en-affil=Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=9
en-affil=Department of Pharmacy, Okayama University Hospital
kn-affil=
en-keyword=Abemaciclib
kn-keyword=Abemaciclib
en-keyword=Adverse event
kn-keyword=Adverse event
en-keyword=Breast cancer
kn-keyword=Breast cancer
en-keyword=Cyclin-dependent kinase 4/6 inhibitor
kn-keyword=Cyclin-dependent kinase 4/6 inhibitor
en-keyword=Palbociclib
kn-keyword=Palbociclib
END