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- 저자 : Chihiro Takei (검색결과 2 건)
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Kaori Matsumoto,Tetsuya Hasegawa,Kosuke Ohara,Chihiro Takei,Masayuki Akimoto 한국약제학회 2020 Journal of Pharmaceutical Investigation Vol.50 No.1
Nabumetone is a prodrug, used as an anti-inflammation agent and having the active metabolite 6-methoxy-2-naphthylacetic acid (6-MNA). The role of the polymorphic enzyme responsible for the 6-O-demethylation of 6-MNA to 6-hydroxy- 2-naphtylacetic acid (6-HNA) was studied using recombinant cytochrome CYP2C9 microsomes (CYP2C9.1, CYP2C9.2 and CYP2C9.3) and human liver microsomes of known genotypes of CYP2C9. Utilizing recombinant CYP2C9.1, Vmax and Vmax/Km values of 6.3 ± 3.3 pmol/min/pmol P450 and 12.4 ± 4.7 nL/min/pmol P450, respectively, were obtained for the 6-MNA metabolism, and were almost similar to those in CYP2C9.2. In contrast, the Vmax/Km value in recombinant CYP2C9.3 was about one-third that of CYP2C9.1. In kinetic studies using liver microsomes of humans genotyped for the CYP2C9 genes, a sample genotyped as *3/*3 revealed about 4- to sixfold lower intrinsic clearance for 6-HNA formation than did samples genotyped as *1/*1. No appreciable differences were observed in kinetic parameters for 6-HNA formation in *1/*2 and *1/*3, while *2/*2 microsomes was comparable to wild type microsomes. In addition, S-warfarin 7-hydroxylation by recombinant CYP2C9.1 and CYP2C9.3 was inhibited by 6-MNA in a mixed manner. The apparent Ki value of 6-MNA on S-warfarin 7-hydroxylation by CYP2C9.3 was higher than that by CYP2C9.1. These results may provide valuable information for optimizing the anticoagulant activity of warfarin when nabumetone is co-administrated to patients.
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Mei Uemura,Yutaka Yano,Toshinari Suzuki,Taro Yasuma,Toshiyuki Sato,Aya Morimoto,Samiko Hosoya,Chihiro Suminaka,Hiromu Nakajima,Esteban C. Gabazza,Yoshiyuki Takei 대한당뇨병학회 2017 Diabetes and Metabolism Journal Vol.41 No.4
patients and institutions. We are developing a glucose area under the curve (AUC) monitoring system without blood sampling using a minimally invasive interstitial fluid extraction technology (MIET). Here we evaluated the accuracy of interstitial fluid glucose (IG) AUC measured by MIET in patients with diabetes for an extended time interval and the potency of detecting hyperglycemia using CGM data as a reference. Methods: Thirty-eight inpatients with diabetes undergoing CGM were enrolled. MIET comprised a pretreatment step using a plastic microneedle array and glucose accumulation step with a hydrogel patch, which was placed on two sites from 9:00 AM to 5:00 PM or from 10:00 PM to 6:00 AM. IG AUC was calculated by accumulated glucose extracted by hydrogel patches using sodium ion as standard. Results: A significant correlation was observed between the predicted AUC by MIET and CGM in daytime (r=0.76) and nighttime (r=0.82). The optimal cutoff for the IG AUC value of MIET to predict hyperglycemia over 200 mg/dL measured by CGM for 8 hours was 1,067.3 mg·hr/dL with 88.2% sensitivity and 81.5% specificity. Conclusion: We showed that 8-hour IG AUC levels using MIET were valuable in estimating the blood glucose AUC without blood sampling. The results also supported the concept of using this technique for evaluating glucose excursion and for screening hyperglycemia during 8 hours in patients with diabetes at any time of day.
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