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

  • Janthima Methaneethorn EMAIL logo , Duangchit Panomvana and Thaveechai Vachirayonstien
Published/Copyright: September 5, 2017

Abstract

Background:

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.

Methods:

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.

Results:

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.

Conclusions:

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.


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

Acknowledgments

We would like to express our sincere gratitude to Dr. Somchai Towanabut for his invaluable guidance throughout the study.

  1. Research funding: None declared.

  2. Employment or leadership: None declared.

  3. Honorarium: None declared.

  4. 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.

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

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Received: 2017-5-11
Accepted: 2017-8-3
Published Online: 2017-9-5
Published in Print: 2017-9-26

©2017 Walter de Gruyter GmbH, Berlin/Boston

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