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Drug Metabolism and Personalized Therapy

Official journal of the European Society of Pharmacogenomics and Personalised Therapy

Editor-in-Chief: Llerena, Adrián

Editorial Board: Benjeddou, Mongi / Chen, Bing / Dahl, Marja-Liisa / Devinsky, Ferdinand / Hirata, Rosario / Hubacek, Jaroslav A. / Ingelman-Sundberg, Magnus / Maitland-van der Zee, Anke-Hilse / Manolopoulos, Vangelis G. / Marc, Janja / Melichar, Bohuslav / Meyer, Urs A. / Nair, Sujit / Nofziger, Charity / Peiro, Ana / Sadee, Wolfgang / Salazar, Luis A. / Simmaco, Maurizio / Turpeinen, Miia / Schaik, Ron / Shin, Jae-Gook / Visvikis-Siest, Sophie / Zanger, Ulrich M.

CiteScore 2018: 1.01

SCImago Journal Rank (SJR) 2018: 0.277
Source Normalized Impact per Paper (SNIP) 2018: 0.446

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Volume 32, Issue 3


Preliminary study of the association between the elimination parameters of phenytoin and phenobarbital

Janthima Methaneethorn
  • Corresponding author
  • Pharmacokinetic Research Unit, Faculty of Pharmaceutical Sciences, Department of Pharmacy Practice, Naresuan University, Phitsanulok, Thailand, Phone: +66 55 961827, Fax: +66 55 963620
  • Center of Excellence for Environmental Health and Toxicology, Naresuan University, Phitsanulok, Thailand
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Duangchit Panomvana
  • Faculty of Pharmaceutical Sciences, Department of Pharmacy Practice, Chulalongkorn University, Bangkok, Thailand
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Thaveechai Vachirayonstien
  • National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani, Thailand
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2017-09-05 | DOI: https://doi.org/10.1515/dmpt-2017-0017



Therapeutic drug monitoring is essential for both phenytoin and phenobarbital therapy given their narrow therapeutic indexes. Nevertheless, the measurement of either phenytoin or phenobarbital concentrations might not be available in some rural hospitals. Information assisting individualized phenytoin and phenobarbital combination therapy is important. This study’s objective was to determine the relationship between the maximum rate of metabolism of phenytoin (Vmax) and phenobarbital clearance (CLPB), which can serve as a guide to individualized drug therapy.


Data on phenytoin and phenobarbital concentrations of 19 epileptic patients concurrently receiving both drugs were obtained from medical records. Phenytoin and phenobarbital pharmacokinetic parameters were studied at steady-state conditions. The relationship between the elimination parameters of both drugs was determined using simple linear regression.


A high correlation coefficient between Vmax and CLPB was found [r=0.744; p<0.001 for Vmax (mg/kg/day) vs. CLPB (L/kg/day)]. Such a relatively strong linear relationship between the elimination parameters of both drugs indicates that Vmax might be predicted from CLPB and vice versa.


Regression equations were established for estimating Vmax from CLPB, and vice versa in patients treated with combination of phenytoin and phenobarbital. These proposed equations can be of use in aiding individualized drug therapy.

Keywords: elimination parameters; epilepsy; phenobarbital; phenytoin


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About the article

Corresponding author: Janthima Methaneethorn, PhD, Pharmacokinetic Research Unit, Faculty of Pharmaceutical Sciences, Department of Pharmacy Practice, Naresuan University, Phitsanulok, Thailand, Phone: +66 55 961827, Fax: +66 55 963620

Received: 2017-05-11

Accepted: 2017-08-03

Published Online: 2017-09-05

Published in Print: 2017-09-26

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Ethical approval: The study protocol was reviewed and approved by the Ethics Committee at Prasart Neurological Institute.

Citation Information: Drug Metabolism and Personalized Therapy, Volume 32, Issue 3, Pages 151–156, ISSN (Online) 2363-8915, ISSN (Print) 2363-8907, DOI: https://doi.org/10.1515/dmpt-2017-0017.

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