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 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=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=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