CVClient

工藤 敏之

クドウ トシユキ  (KUDO TOSHIYUKI)

基本情報

所属
武蔵野大学 薬学部 薬学科 講師
学位
学士(星薬科大学)
修士(星薬科大学大学院)
博士(星薬科大学大学院)

J-GLOBAL ID
201701007072398063
researchmap会員ID
B000270073

研究キーワード

 1

経歴

 4

学歴

 4

委員歴

 2

論文

 68
  • Kenjiro Okubo, Toshiyuki Kudo, Sae Yoshihara, Yu Nakabayashi, Kana Nakauchi, Akimi Tanaka, Moe Saito, Ayumi Tsujisawa, Hitomi Goda, Yoshiaki Yamagishi, Chinatsu Otake, Kosho Makino, Hideyo Takahashi, Kiyomi Ito
    Drug Metabolism and Pharmacokinetics 54 100537-100537 2024年2月  
  • Tomohisa Nakada, Toshiyuki Kudo, Kiyomi Ito
    Drug metabolism and disposition: the biological fate of chemicals 2023年3月1日  
    Creatinine is a common biomarker of renal function and is secreted in the renal tubular cells via drug transporters such as organic cation transporter 2 and multidrug and toxin extrusion (MATE) 1/2-K. To differentiate between drug-induced acute kidney injury (AKI) and drug interactions through the renal transporter, it has been examined whether these transporter inhibitions quantitatively explained increases in serum creatinine (SCr) at their clinically relevant concentrations using drugs without any changes in renal function. For such renal transporter inhibitors and recently approved tyrosine kinase inhibitors (TKIs), this mini-review describes clinical increases in SCr and inhibitory potentials against the renal transporters. Most cases of SCr elevations can be explained by considering the renal transporter inhibitions based on unbound maximum plasma concentrations, except for drugs associated with obvious changes in renal function. SCr increases for cobicistat, dolutegravir, and dronedarone, and some TKIs were significantly underestimated, and these underestimations were suggested to be associated with low plasma unbound fractions. Sensitivity analysis of SCr elevations regarding inhibitory potentials of MATE1/2-K demonstrated that typical inhibitors such as cimetidine, DX-619, pyrimethamine, and trimethoprim could give false interpretations of AKI according to the criteria based on relative or absolute levels of SCr elevations. Recent progress and current challenges of physiologically-based pharmacokinetics modeling for creatinine disposition were also summarized. Although it should be noted for the potential impact of in vitro assay designs on clinical translatability of transporter inhibitions data, mechanistic approaches could support decision-making in clinical development to differentiate between AKI and creatinine-drug interactions. Significance Statement Serum creatinine (SCr) is widely used as an indicator of kidney function, but it increases due to inhibitions of renal transporters such as multidrug and toxin extrusion protein ½-K despite no functional changes in the kidney. Such SCr elevations were quantitatively explained by renal transporter inhibitions except for some drugs with high protein binding. The present analysis demonstrated that clinically relevant inhibitors of the renal transporters could cause SCr elevations above levels corresponding to acute kidney injury criteria.
  • Toshiyuki Hikita, Hitomi Goda, Yasuko Ogawa, Toshiyuki Kudo, Kiyomi Ito
    Pediatrics international : official journal of the Japan Pediatric Society 65(1) e15429 2023年1月  
    BACKGROUND: Caffeine consumption is a risk factor for chronic daily headache but few studies have addressed relationships between pediatric patient caffeine levels and headache severity. We examined associations between serum and urine caffeine levels and headache severity in childhood and adolescent migraine cases. METHODS: Levels of caffeine and caffeine metabolites in serum and urine samples were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The Wilcoxon rank-sum test was used for comparisons of age, sleep time, headache severity, caffeine consumption, and caffeine detection. Spearman's rank correlation coefficient (ρ) was calculated for associations. Correlations where ρ ≥ 0.3 and differences where p < 0.05 were considered statistically significant. RESULTS: Of the 40 patients studied, 34 declared caffeine consumption and six declared no caffeine consumption. These two groups did not differ significantly in any of the above clinical parameters. Liquid chromatography-tandem mass spectrometry analysis of both serum and urine samples revealed nine caffeine-negative (level <0.0625 μM) and 31 caffeine-positive cases. The Headache Impact Test-6 (HIT-6) score was higher (p = 0.033) for the caffeine-positive group versus the caffeine-negative group. Caffeine was detected by LC-MS/MS in the serum and/or urine of three of the six patients who declared no caffeine consumption. No significant correlations were observed among age, sleep times, headache severity score, or levels of caffeine and caffeine metabolites. CONCLUSION: Thirty one of 40 (77.5%) cases of childhood/ adolescence migraine showed serum and urine caffeine positivity based on LC-MS/MS. The HIT-6 score, a measure of headache severity, was significantly higher for caffeine-positive versus caffeine-negative cases. Symptoms of childhood/adolescence migraine were exacerbated by caffeine consumption.
  • 川野 久美, 工藤 敏之, 前田 和哉, 嶋田 努, 水野 尚美
    薬剤学: 生命とくすり 82(3) 121-125 2022年7月  
  • Kentaro Ohta, Nobuko Matsushima, Hiromi Tanii, Herta Crauwels, Toshiyuki Kudo, Kiyomi Ito
    Drug metabolism and pharmacokinetics 41 100422-100422 2021年12月  
    Rilpivirine is a non-nucleoside reverse transcriptase inhibitor, used for the treatment of human immunodeficiency virus type-1 infection. An open label study was conducted to investigate the pharmacokinetics (PK) and safety of a single oral dose of rilpivirine 25 mg in Japanese healthy adult subjects. No adverse events were reported. The mean Cmax (144.3 ng/mL) and AUCinf (4542 ng h/mL) in Japanese subjects were approximately 30 % higher than those reported from a similar study in Caucasian healthy subjects, whereas the median tmax and mean t1/2 values were comparable between studies. A simple physiologically based PK model was developed to characterize the rilpivirine PK profile. The model adequately described rilpivirine PK profiles, and well-predicted drug-drug interactions. With exploration using the model, body size and CYP3A4 abundance were identified as factors which explained the observed inter-ethnic difference in rilpivirine exposure. The inter-ethnic difference in rilpivirine exposure was however considered not clinically relevant, since inter-individual variabilities of those intrinsic factors are larger than inter-ethnic ones; and the observed AUCinf in Japanese subjects was within the range of AUCtau associated with efficacy and safety in Phase 3 studies. This study results support the use of rilpivirine without dose modification specific to Japanese patients.

MISC

 17

書籍等出版物

 7

講演・口頭発表等

 142

担当経験のある科目(授業)

 3

共同研究・競争的資金等の研究課題

 8

資格・免許

 1
  • 件名
    薬剤師免許
    年月日
    2005/06/16
    概要
    第397586