Dose adjustment of phenytoin for comedication in Japanese patients with epilepsy

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/27477
Title
Dose adjustment of phenytoin for comedication in Japanese patients with epilepsy
File
Description

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 x 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 (> or =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.

(医博乙265)

Author
著者 福岡 憲泰
著者(ヨミ) フクオカ ノリヤス
著者(別表記) Fukuoka Noriyasu
Publication Title
Therapeutic Drug Monitoring
Publication Title Alternative
Ther Drug Monit.
Volume
31
Issue
1
Start Page
57
End Page
62
Publisher
International Association of Therapeutic Drug Monitoring and Clinical Toxicology
Lippincott, Williams & Wilkins
Published Date
2009-02
ISSN
0163-4356
NCID
AA00459801
PMID
19077928
DOI
10.1097/FTD.0b013e3181947772
Resource Type
Thesis or Dissertation
Language
eng
Resource URL
https://doi.org/10.1097/FTD.0b013e3181947772
Text Version
none
Grant ID
博乙第265号
Grant Date
2013-11-20
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
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