Wiley Acta Medica Okayama 0306-5251 2025 Comprehensive analysis of adverse event profile changes with pertuzumab addition to trastuzumab‐based breast cancer therapy: Disproportionality analysis using VigiBase EN Tatsuaki Takeda Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Jun Matsumoto Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Tomonori Sakai Department of Pharmacy, Okayama University Hospital Naohiro Iwata Department of Pharmacy, Okayama University Hospital Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Toshihiro Koyama Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Noritaka Ariyoshi Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Yoshito Zamami Department of Pharmacy, Okayama University Hospital Aims: Pertuzumab is used in combination with trastuzumab-based therapy for HER2-positive breast cancer. However, real-world safety information on pertuzumab remains limited. This study assessed the safety of adding pertuzumab to trastuzumab-based therapy for HER2-positive breast cancer using real-world data. Methods: VigiBase, the World Health Organization's global database of adverse events (AEs), containing reports from November 1967 to December 2023, was used. Signals for pertuzumab-associated AEs in breast cancer cases were detected using the reporting odds ratio (ROR). Results: Signals of trastuzumab plus pertuzumab relative to trastuzumab alone were detected in gastrointestinal disorders (ROR: 1.45, 95% confidence interval: 1.26–1.67), including diarrhoea (3.49, 2.83–4.30); infections and infestations (1.54, 1.24–1.91); and skin and subcutaneous tissue disorders (ROR: 1.63, 1.40–1.90), including pruritus (1.96, 1.51–2.55) and rash (1.63, 1.20–2.23). Further, signals of trastuzumab plus docetaxel plus pertuzumab relative to those of trastuzumab plus docetaxel were detected in gastrointestinal disorders (1.63, 1.38–1.93), including nausea (1.72, 1.24–2.39) and vomiting (1.48, 1.01–2.17), and in nervous system disorders (1.50, 1.20–1.87), including paraesthesia (2.60, 1.33–5.08) and peripheral sensory neuropathy (5.94, 1.79–19.71). The frequency of AEs causing or prolonging hospitalization was increased with trastuzumab plus pertuzumab compared to that with trastuzumab alone (1.18, 1.00–1.38). Conclusions: AE profiles after the addition of pertuzumab to trastuzumab-based therapy were comprehensively identified. The findings in this study highlight the importance of considering these AEs when selecting pertuzumab combination therapy to ensure the safety of patients with breast cancer. No potential conflict of interest relevant to this article was reported.

Pharmaceutical Society of Japan Acta Medica Okayama 0031-6903 145 1 2025 薬物代謝酵素の発現情報を活用した腎がん治療の個別適正化 7 14 EN Jun Matsumoto Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Notable advances have recently been achieved in drug therapies for renal cell carcinoma (RCC). Several tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have been approved for metastatic RCC (mRCC). The current first-line treatment for mRCC involves combination therapies using TKIs and ICIs. However, there is no consensus on which TKI+ICI therapy is best or how to select the appropriate therapy for individual patients with RCC. The kidney expresses various metabolic enzymes, including CYP and uridine diphosphate glucose (UDP)-glucuronosyltransferase (UGT). Although information on CYP and UGT expression in the kidney is limited compared to our understanding of liver expression, the main CYP and UGT subtypes expressed at high levels in the kidney are estimated to be CYP2B6, CYP3A5, CYP4A11, CYP4F2, UGT1A6, UGT1A9, and UGT2B7. In RCC, the expression profiles and levels of these enzymes are somewhat altered compared with normal kidney. The main known subtypes of CYP and UGT in RCC are CYP1B1, CYP3A5, CYP4A11, UGT1A6, UGT1A9, UGT1A10, and UGT2B7. High CYP expression has been reported in several cancers, possibly conferring resistance to anti-cancer drugs including TKIs, due to extensive drug metabolism. Additionally, CYP and UGT expression levels may possibly affect cancer prognosis by metabolizing endogenous substrates, regardless of their role in anti-cancer drug metabolism. In this review, I discuss CYP and UGT expression level profiles in RCC based on previously published papers, including ours, and examine possible relationships between these enzyme expression profiles and treatment outcomes for patients with RCC. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2210-7703 46 2 2024 A comparison between the adverse event profiles of patients receiving palbociclib and abemaciclib: analysis of two real-world databases 536 541 EN Tatsuaki Takeda Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Shiho Sugimoto Department of Personalized Medicine and Preventive Healthcare Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Matsumoto Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Naohiro Iwata Department of Pharmacy, Okayama University Hospital Akihiko Nakamoto Department of Pharmacy, Okayama University Hospital Aya Fukuma Ozaki Department of Clinical Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University of California Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Noritaka Ariyoshi Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Yoshito Zamami Department of Pharmacy, Okayama University Hospital 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. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0300-8177 478 8 2022 Significance of UGT1A6, UGT1A9, and UGT2B7 genetic variants and their mRNA expression in the clinical outcome of renal cell carcinoma 1779 1790 EN Jun Matsumoto Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Anzu Nishimoto Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shogo Watari Department of Urology, National Hospital Organization Okayama Medical Center Hideo Ueki Department of Urology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Shoya Shiromizu Department of Pharmacy, Okayama University Hospital Naohiro Iwata Department of Pharmacy, Okayama University Hospital Tatsuaki Takeda Department of Pharmacy, Okayama University Hospital Soichiro Ushio Department of Pharmacy, Okayama University Hospital Makoto Kajizono Department of Pharmacy, Okayama University Hospital Masachika Fujiyoshi Department of Pharmacy, Tottori University Hospital Toshihiro Koyama Department of Pharmaceuticals Biomedicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Motoo Araki Department of Urology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Koichiro Wada Department of Urology, Faculty of Medicine, Shimane University Yoshito Zamami Department of Pharmacy, Okayama University Hospital Yasutomo Nasu Department of Urology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Noritaka Ariyoshi Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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. No potential conflict of interest relevant to this article was reported.

Elsevier Ltd. Acta Medica Okayama 13474367 40 2021 Blood concentrations of tacrolimus upon conversion from rabeprazole to vonoprazan in renal transplant recipients: Correlation with cytochrome P450 gene polymorphisms 100407 EN Shogo Watari Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoo Araki Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Matsumoto Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kasumi Yoshinaga Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takanori Sekito Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Maruyama Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yosuke Mitsui Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takuya Sadahira Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Risa Kubota Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shingo Nishimura Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koichiro Wada Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuyuki Kobayashi Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hidemi Takeuchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Katsuyuki Tanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Masashi Kitagawa Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Hiroshi Morinaga Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Shinji Kitamura Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Hitoshi Sugiyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Noritaka Ariyoshi Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Masami Watanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Toyohiko Watanabe Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasutomo Nasu Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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. No potential conflict of interest relevant to this article was reported.

International Institute of Anticancer Research Acta Medica Okayama 0250-7005 41 5 2021 Relevance of CYP3A5 Expression on the Clinical Outcome of Patients With Renal Cell Carcinoma 2511 2521 EN Jun Matsumoto Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yumi Kotera Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shogo Watari Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koichi Takeuchi Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hideo Ueki Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshihiro Koyama Department of Pharmaceuticals Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koichiro Wada Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masachika Fujiyoshi Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasutomo Nasu Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Noritaka Ariyoshi Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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. No potential conflict of interest relevant to this article was reported.

Japan Society of Human Genetics Acta Medica Okayama 1434-5161 65 2019 Effect of CYP3A5*3 genetic variant on the metabolism of direct-acting antivirals in vitro : a different effect on asunaprevir versus daclatasvir and beclabuvir 143 153 EN Jun Matsumoto Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate Su Nwe San Department of Pharmacokinetics, Pharmaceutical Sciences, International University of Health and Welfare Masachika Fujiyoshi Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate Ayano Kawauchi Department of Pharmacokinetics, Pharmaceutical Sciences, International University of Health and Welfare Natsumi Chiba Department of Pharmacokinetics, Pharmaceutical Sciences, International University of Health and Welfare Ran Tagai Department of Pharmacokinetics, Pharmaceutical Sciences, International University of Health and Welfare Ryoko Sanbe Department of Pharmacokinetics, Pharmaceutical Sciences, International University of Health and Welfare Shiho Yanaka Department of Pharmacokinetics, Pharmaceutical Sciences, International University of Health and Welfare Hiroaki Sakaue Department of Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences Yoshinori Kato Department of Pharmacokinetics, Pharmaceutical Sciences, International University of Health and Welfare Hiroyoshi Nakamura Department of Pharmacokinetics, Pharmaceutical Sciences, International University of Health and Welfare Harumi Yamada Department of Pharmacokinetics, Pharmaceutical Sciences, International University of Health and Welfare Noritaka Ariyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama University 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. No potential conflict of interest relevant to this article was reported.

TAYLOR & FRANCIS Acta Medica Okayama 00498254 49 8 2018 Minor contribution of CYP3A5 to the metabolism of hepatitis C protease inhibitor paritaprevir in vitro 935 944 EN Su Nwe San Graduate School of Pharmaceutical Sciences, International University of Health and Welfare Jun Matsumoto Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama University Yumi Saito Department of Pharmaceutical Sciences, School of Pharmacy , International University of Health and Welfare Masako Koike Department of Pharmaceutical Sciences, School of Pharmacy , International University of Health and Welfare Hiroaki Sakaue Department of Biochemistry, School of Pharmacy , Tokyo University of Pharmacy and Life Sciences Yoshinori Kato Department of Pharmaceutical Sciences, School of Pharmacy , International University of Health and Welfare Masachika Fujiyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama University Noritaka Ariyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama University Harumi Yamada Department of Pharmaceutical Sciences, School of Pharmacy , International University of Health and Welfare 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. No potential conflict of interest relevant to this article was reported.

Elsevier B.V. Acta Medica Okayama 21867070 8 2019 A proposed simple screening method to determine relative contributions of CYP3A4 and CYP3A5 to drug metabolism in vitro 41 44 EN Jun Matsumoto Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyoshi Nakamura Department of Pharmaceutical Sciences, International University of Health and Welfare Su Nwe San Graduate School of Pharmaceutical Sciences, International University of Health and Welfare Hikari Sato Department of Pharmaceutical Sciences, International University of Health and Welfare Manami Takezawa Department of Pharmaceutical Sciences, International University of Health and Welfare Ryuto Kishi Department of Pharmaceutical Sciences, International University of Health and Welfare Yutaro Kito Department of Pharmaceutical Sciences, International University of Health and Welfare Junko Sugano Department of Pharmaceutical Sciences, International University of Health and Welfare Mai Izuki Department of Pharmaceutical Sciences, International University of Health and Welfare Nao Yanagisawa Department of Pharmaceutical Sciences, International University of Health and Welfare Naoki Ikeda Department of Pharmaceutical Sciences, International University of Health and Welfare Yusuke Saito Department of Pharmaceutical Sciences, International University of Health and Welfare Yoshinori Kato Department of Pharmaceutical Sciences, International University of Health and Welfare Harumi Yamada Department of Pharmaceutical Sciences, International University of Health and Welfare Masachika Fujiyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Noritaka Ariyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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. No potential conflict of interest relevant to this article was reported.