Details of a Researcher - AKAMINE Yumiko

Hayato Yokota, Yumiko Akamine, Harumi Hatakeyama, Hideaki Kagaya, Sho Sakamoto, Mitsuru Saito, Masahide Takeda, Kazuhiro Sato, Katsutoshi Nakayama, Masafumi Kikuchi

Journal of pharmaceutical health care and sciences ( Journal of Pharmaceutical Health Care and Sciences ) 11 ( 1 ) 20 - 20 2025.03

Research paper (journal)

BACKGROUND: Azole antifungals are the standard treatment for pulmonary mycosis, which may develop during long-term immunotherapy for kidney transplant. Isavuconazole (ISCZ) is a cytochrome P450 (CYP) 3 A inhibitor that has a risk of interacting with the immunosuppressive drug tacrolimus (TAC). We report a case of simple pulmonary aspergilloma with renal dysfunction due to increased trough levels of TAC after ISCZ coadministration. CASE PRESENTATION: A male in his 60s was treated with TAC 3.0 mg/day orally to prevent graft rejection after kidney transplantation. He received a loading dose of ISCZ 600 mg/day orally for two days, followed by a maintenance dose of 200 mg/day for simple pulmonary aspergilloma. The TAC trough concentration increased markedly from 2.4 to 9.9 ng/mL on day 6 after coadministration. The creatinine level increased from 0.70 to 1.08 mg/dL, suggesting renal dysfunction due to TAC. Subsequently, the TAC dosage was reduced, leading to a decreased blood TAC concentration and improved renal function. The patient's genotype was CYP3A5*1/*3. CONCLUSIONS: In the early stages of ISCZ treatment, the blood TAC concentration is higher, and CYP3A5 polymorphisms may partially explain the extent of this interaction. We recommend more careful monitoring of TAC and serum creatinine levels for approximately one week after ISCZ administration.

DOI PubMed

Influence of interleukin-6 on the pharmacokinetics and pharmacodynamics of osimertinib in patients with non-small cell lung cancer.

Hayato Yokota, Kazuhiro Sato, Sho Sakamoto, Yuji Okuda, Masahide Takeda, Yumiko Akamine, Katsutoshi Nakayama, Masatomo Miura

Cancer chemotherapy and pharmacology ( Cancer Chemotherapy and Pharmacology ) 95 ( 1 ) 49 - 49 2025.03

Research paper (journal)

PURPOSE: The inflammatory cytokine interleukin (IL)-6 reduces the activity of drug metabolic enzymes and promotes tumor progression. We investigated the effect of IL-6 on the pharmacokinetics of osimertinib and the association between an IL-6 polymorphism and clinical outcomes in 30 patients with non-small cell lung cancer (NSCLC). METHODS: Osimertinib and IL-6 plasma concentrations were measured on day 15 after therapy initiation. The genotype of IL-6 1800796G > C was identified using polymerase chain reaction-restriction fragment length polymorphism. Risk factors affecting overall survival (OS) were assessed by Cox proportional hazard regression analysis. RESULTS: The IL-6 concentration was significantly correlated with the osimertinib trough plasma concentration (r = 0.423, P = 0.020) and area under the plasma concentration-time curve (r = 0.420, P = 0.021). The IL-6 concentration was significantly higher in patients with the IL-6 rs1800796G allele versus C/C genotype (P = 0.024). OS was significantly shorter in patients with the IL-6 rs1800796G allele versus C/C genotype (median: 15.1 vs. 48.9 months, P = 0.005). Univariate and multivariate analyses indicated that the IL-6 rs1800796G allele is an independent risk factor for OS (crude hazard ratio = 7.07; P = 0.014; adjusted hazard ratio = 6.38; P = 0.021). CONCLUSION: A higher IL-6 concentration was associated with reduced metabolic activity of osimertinib, leading to increased osimertinib exposure. As the IL-6 concentration was higher in NSCLC patients with the IL-6 rs1800796G allele, it might be an independent prognostic factor for patients treated with osimertinib.

DOI PubMed

Effects of CYP3A5 polymorphism and renal impairment on the drug interaction between venetoclax and fluconazole in acute myeloid leukaemia patients.

Takahiro Kobayashi, Honami Sato, Yumiko Akamine, Yayoi Fukushi, Naoto Takahashi, Masatomo Miura

Xenobiotica; the fate of foreign compounds in biological systems ( Xenobiotica ) 55 ( 1 ) 1 - 6 2024.12

Research paper (journal)

The aim of this study was to investigate the effects of renal function and CYP3A5 polymorphism on the drug interaction between venetoclax and fluconazole in thirty acute myeloid leukaemia patients.The area under the plasma concentration-time curve (AUC) and trough concentration (C0) of venetoclax and the fluconazole C0 were obtained from plasma samples on day 7 later after initiation of venetoclax 200 mg/day combined with fluconazole.The fluconazole C0 values in patients with moderate and severe renal impairment were significantly higher than those in patients with normal or mild impairment (median values 7037, 6234, and 4813 ng/mL, respectively, P = 0.026).In patients with CYP3A5*3/*3 genotype, the AUC0-24 and C0 of venetoclax were not associated with fluconazole C0; however, in patients with a CYP3A5*1 allele, a significant positive correlation was observed between venetoclax C0 and fluconazole C0 (r = 0.782, P = 0.004).The metabolism of venetoclax by CYP3A4 is inhibited even at low fluconazole C0. In patients with a CYP3A5*1 allele, CYP3A5 is inhibited when high fluconazole C0 is induced by renal impairment.The dose of fluconazole for prophylaxis may be 100 mg in patients with severe renal impairment receiving venetoclax therapy.

DOI PubMed

Naldemedine-induced perforation of a diverticulum in the sigmoid colon of a patient with opioid-related constipation: a case report.

Hayato Yokota, Yumiko Akamine, Mizuki Kobayashi, Takuro Kitabayashi, Misato Horie, Tentaro Endo, Takechiyo Yamada, Masafumi Kikuchi

Journal of pharmaceutical health care and sciences ( Journal of Pharmaceutical Health Care and Sciences ) 10 ( 1 ) 2024.08

Research paper (journal)

BACKGROUND: Naldemedine is an orally available peripherally acting μ-opioid receptor antagonist approved to treat opioid-induced constipation (OIC). It is contraindicated for patients with known or suspected gastrointestinal obstruction to protect against naldemedine-induced perforation. Here, we report a clinical case of suspected perforation of a diverticulum in the sigmoid colon associated with naldemedine. CASE PRESENTATION: The patient was a 65-year-old man with a history of oral cancer who had been prescribed oxycodone (20 mg/day) for cancer pain. On day 0, the patient started naldemedine 0.2 mg once daily before bedtime for OIC. The dose of oxycodone was increased for pain control up to 60 mg/day. On day 35 of naldemedine treatment, the patient developed fever and abdominal pain, and his frequency of defecation had decreased. Initial laboratory results showed a C-reactive protein (CRP) level of 28.5 mg/dL and white blood cell (WBC) count of 13,500/µL. On day 37, the patient still had tenderness in his lower abdomen. Abdominal computed tomography revealed free air in the abdominal cavity suggesting an intestinal perforation. A Hartmann procedure was performed. Histopathological findings showed numerous diverticula in the sigmoid colon, some of which were perforated. CONCLUSIONS: These results suggest that the effects of OIC may have compressed the intestinal tract, which was followed by naldemedine-activation of peristalsis, which led to the onset of intestinal perforation. In patients with pre-existing diverticular disease, we should monitor for increased WBC counts and CRP levels after the initiation of treatment with naldemedine, and consider performing appropriate tests early in the event of abdominal complaints.

DOI PubMed

Association of the modified Glasgow prognostic score and prognostic nutritional index with duration of oral anamorelin administration in patients with cancer cachexia: a retrospective cohort study.

Kazuma Fujita, Yumiko Akamine, Haruka Igarashi, Yayoi Fukushi, Katsuya Sasaki, Koji Fukuda, Masafumi Kikuchi, Hiroyuki Shibata

Japanese journal of clinical oncology ( Japanese Journal of Clinical Oncology ) 54 ( 11 ) 1165 - 1170 2024.06

Research paper (journal)

BACKGROUND: The modified Glasgow Prognostic Score (mGPS) and Prognostic Nutritional Index (PNI) are indicators of nutritional status in cancer patients; however, the effects of baseline mGPS and PNI on the duration of administration of the ghrelin receptor agonist anamorelin, which is used to treat cachexia in patients with cancer, are unclear. This study aimed to clarify the association of mGPS and PNI with the duration of oral anamorelin administration for patients who did not have beneficial effects from anamorelin. METHODS: The attending physician determined the duration of oral anamorelin administration based on discontinuation due to cancer progression, poor efficacy, adverse events, or death. RESULTS: The 12-week continuation rate of oral anamorelin was 30.4%. Univariate analysis revealed that an Eastern Cooperative Oncology Group performance status (ECOG-PS) of ≥2 (P < .001), concurrent chemotherapy (P = .002), albumin level (P = .005), C-reactive protein level (P = .013), and a mGPS of 2 (P = .014) were statistically significant predictors of the 12-week continuation rate of oral anamorelin. In the multivariate analysis, a mGPS of 2 remained a significant risk factor, and the ECOG-PS and concurrent chemotherapy had no effect on the association between the mGPS and 12-week continuation rate of oral anamorelin. CONCLUSION: Patients with a mGPS of 2, compared with mGPS of 0 or 1, are less likely to maintain oral anamorelin therapy, regardless of the ECOG-PS or concurrent chemotherapy. Therefore, it is necessary to consider initiating anamorelin administration at mGPS 0 or 1.

DOI PubMed

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An update on the clinical pharmacokinetics of fexofenadine enantiomers.

Akamine Y and Miura M.

Expert Opinion on Drug Metabolism & Toxicology ( Taylor and Francis Group ) 2018.04

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Evaluation of the accuracy of simultaneous determination of plasma concentrations of clozapine and N-desmethylclozapine using the new LM1010 high performance liquid chromatography.

赤嶺由美子, 松下美由紀, 森川悟, 三浦昌朋

臨床精神薬理 28 ( 1 ) 87 - 98 2025.01

J-GLOBAL

Simultaneous Determination of Serum Concentrations of Phenytoin and Carbamazepine with LM1010 High-Performance Liquid Chromatography and Comparison with CLIA

Akamine Yumiko, Matsushita Miyuki, Morikawa Satoru, Miura Masatomo

Iryo Yakugaku (Japanese Journal of Pharmaceutical Health Care and Sciences) ( Japanese Society of Pharmaceutical Health Care and Sciences ) 50 ( 9 ) 465 - 472 2024.09

DOI CiNii Research

Determination of Plasma Concentrations of Imatinib by a Novel Automated Analyzer Based on High-Performance Liquid Chromatography

福司弥生, 赤嶺由美子, 松下美由紀, 森川悟, 三浦昌朋, 三浦昌朋

YAKUGAKU ZASSHI (Web) 143 ( 11 ) 2023

J-GLOBAL

赤嶺由美子

臨床精神薬理 25 ( 1 ) 83 - 88 2022.01

CiNii Research J-GLOBAL

Personalized therapy of Psychotropic Drugs based on Pharmacokinetics-Related Biomarkers

赤嶺由美子

日本臨床精神神経薬理学会プログラム・抄録集 31st 2021

J-GLOBAL