| Item type |
学位論文 / Thesis or Dissertation(1) |
| 公開日 |
2015-12-04 |
| タイトル |
|
|
タイトル |
Influence of NAT2 polymorphisms on sulfamethoxazole pharmacokinetics in renal transplant recipients |
| 言語 |
|
|
言語 |
jpn |
| 資源タイプ |
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|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_db06 |
|
資源タイプ |
doctoral thesis |
| アクセス権 |
|
|
アクセス権 |
open access |
|
アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 別タイトル |
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|
その他のタイトル |
腎移植患者におけるスルファメトキサゾールの体内動態に及ぼすNAT2 遺伝子多型の影響 |
| 作成者 |
加賀谷, 英彰
KAGAYA, Hideaki
|
| 内容記述（抄録） |
|
|
内容記述タイプ |
Other |
|
内容記述 |
The sulfamethoxazole (SMX)-trimethoprim drug combination is routinely used as prophylaxis against Pneumocystis pneumonia during the first 3 to 6 months after renal transplantation. The objective of this study was to examine the impact of N-acetyltransferase 2 (NAT2) and CYP2C9 polymorphisms on the pharmacokinetics of SMX in 118 renal transplant recipients. Starting on day 14 after renal transplantation, patients were administered 400 mg/day-80 mg/day of SMX-trimethoprim orally once daily. On day 14 after the beginning of SMX therapy, plasma SMX concentrations were determined by a high-performance liquid chromatography method. The SMX area under the concentration-time curve from 0 to 24 h (AUC0-24) for 15 recipients with the NAT2 slow acetylator genotype (NAT2*5/*6, -*6/*6, -*6/*7, and -*7/*7) was significantly greater than that for 56 recipients with the NAT2 rapid acetylator genotype (homozygous for NAT2*4) (766.4 ± 432.3 versus 537.2 ± 257.5 μg-h/ml, respectively; P = 0.0430), whereas there were no significant differences in the SMX AUC0-24 between the CYP2C9*1/*1 and -*1/*3 groups. In a multiple regression analysis, the SMX AUC0-24 was associated with NAT2 slow acetylator polymorphisms (P = 0.0095) and with creatinine clearance (P = 0.0499). Hepatic dysfunction in NAT2 slow acetylator recipient patients during the 6-month period after SMX administration was not observed. SMX plasma concentrations were affected by NAT2 polymorphisms and renal dysfunction. Although standard SMX administration to patients with NAT2 slow acetylator polymorphisms should be accompanied by monitoring for side effects and drug interaction effects from the inhibition of CYP2C9, SMX administration at a low dose (400 mg) as prophylaxis may not provide drug concentrations that reach the level necessary for the expression of side effects. Further studies with a larger sample size should be able to clarify the relationship between SMX plasma concentration and side effects. |
| 著者版フラグ |
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|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| 書誌情報 |
発行日 2015-11-01
|
| 出版者 |
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|
出版者 |
秋田大学 |
| 備考 |
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|
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秋田大学審査学位論文(Antimicrobial Agents and Chemotherapy,56(2) p825-p829掲載論文) |
| 学位名 |
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|
学位名 |
博士（医学） |
| 学位授与機関 |
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学位授与機関識別子Scheme |
kakenhi |
|
|
学位授与機関識別子 |
11401 |
|
|
学位授与機関名 |
秋田大学 |
| 学位授与年月日 |
|
|
学位授与年月日 |
2015-09-24 |
| 学位授与番号 |
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|
学位授与番号 |
乙第638号 |
内容要旨及び審査結果要旨 (977.6 kB)
