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Dose adjustment of phenytoin for comedication in Japanese patients with epilepsy
https://kagawa-u.repo.nii.ac.jp/records/209
https://kagawa-u.repo.nii.ac.jp/records/209588cd623-674a-4b54-a27c-6c3833f78c5c
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内容の要旨 (331.5 kB)
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審査の結果の要旨 (296.3 kB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||||
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公開日 | 2013-11-20 | |||||||||||
タイトル | ||||||||||||
タイトル | Dose adjustment of phenytoin for comedication in Japanese patients with epilepsy | |||||||||||
言語 | en | |||||||||||
言語 | ||||||||||||
言語 | eng | |||||||||||
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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 | |||||||||||
著者 |
福岡, 憲泰
× 福岡, 憲泰
WEKO
2631
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内容記述タイプ | Abstract | |||||||||||
内容記述 | Abstract This study sought a suitable physiological parameter related to daily phenytoin (PHT) dose (D) providing a steady-state serum concentration (Ct) and analyzed the influences of coadministered antiepileptic drugs on Ct quantitatively to adjust PHT dose. Data were derived from a total of 368 patients with epilepsy treated with multiple oral administrations of PHT. Phenobarbital, carbamazepine, valproic acid, zonisamide, clonazepam, and ethosuximide were coadministered. For the administration of PHT alone, 4 types of parameter, that is, total body weight, total body water volume, body surface area, and extracellular water volume (VECW) were examined. Then, a Michaelis-Menten kinetic model was postulated including VECW, which was assumed to detect the effect of the coadministered drug quantitatively. Adopting VECW as a transforming factor, the concentration to dose (L:D) ratio [Ct/(D/VECW)] was independent of the patient's age and gender in relation to Ct and expressed as Ct/(D/VECW) = 0.0245 × Ct + 0.076. Analysis clarified that ratios were estimated as 0.90, 0.91, 0.89, and 0.84 for phenobarbital, carbamazepine, valproic acid, and zonisamide, respectively, to maintain the same Ct concentration of PHT. Influences were not detected as the number (≧2) of coadministered drugs increased, regardless of factor type. PHT clearance changed in an age-dependent manner and was usually poorly correlated with weight-based doses. VECW was more closely correlated with age-dependent changes in physiological parameters such as clearance. VECW was considered to remove the influence of age on clearance, and estimated ratios could be used for all age groups. In the case of the addition or removal of concomitant treatment with antiepileptic drugs in the same patient, the daily PHT dose was calculated using the value of each ratio or its reciprocal. Our results could be helpful in determining PHT dosing. |
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言語 | en | |||||||||||
学位名 | ||||||||||||
言語 | ja | |||||||||||
学位名 | 博士(医学) | |||||||||||
学位授与機関 | ||||||||||||
学位授与機関識別子Scheme | kakenhi | |||||||||||
学位授与機関識別子 | 16201 | |||||||||||
言語 | ja | |||||||||||
学位授与機関名 | 香川大学 | |||||||||||
言語 | en | |||||||||||
学位授与機関名 | Kagawa University | |||||||||||
学位授与年月日 | ||||||||||||
学位授与年月日 | 2013-11-20 | |||||||||||
学位授与番号 | ||||||||||||
学位授与番号 | 乙第265号 | |||||||||||
権利 | ||||||||||||
言語 | en | |||||||||||
権利情報 | © 2009 Lippincott Williams & Wilkins, Inc. | |||||||||||
PubMed番号 | ||||||||||||
識別子タイプ | PMID | |||||||||||
関連識別子 | 19077928 | |||||||||||
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関連タイプ | isVersionOf | |||||||||||
識別子タイプ | DOI | |||||||||||
関連識別子 | https://doi.org/10.1097/ftd.0b013e3181947772 | |||||||||||
キーワード | ||||||||||||
言語 | en | |||||||||||
主題Scheme | Other | |||||||||||
主題 | phenytoin | |||||||||||
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言語 | en | |||||||||||
主題Scheme | Other | |||||||||||
主題 | transforming factor | |||||||||||
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言語 | en | |||||||||||
主題Scheme | Other | |||||||||||
主題 | Michaelis-Menten model | |||||||||||
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言語 | en | |||||||||||
主題Scheme | Other | |||||||||||
主題 | extracellular water volume | |||||||||||
キーワード | ||||||||||||
言語 | en | |||||||||||
主題Scheme | Other | |||||||||||
主題 | therapeutic drug monitoring | |||||||||||
KEID | ||||||||||||
値 | 27477 |