Original Research

Therapeutic drug monitoring of phenytoin and valproic acid in critically ill patients at Windhoek Central Hospital, Namibia

Bonifasius S. Singu, Helen Morrison, Lydia Irengeya, Roger K. Verbeeck
African Journal of Laboratory Medicine | Vol 11, No 1 | a1628 | DOI: https://doi.org/10.4102/ajlm.v11i1.1628 | © 2022 Bonifasius S. Singu, Helen Morrison, Lydia Irengeya, Roger K. Verbeeck | This work is licensed under CC Attribution 4.0
Submitted: 22 May 2021 | Published: 21 July 2022

About the author(s)

Bonifasius S. Singu, School of Pharmacy, Faculty of Health Sciences, University of Namibia, Windhoek, Namibia
Helen Morrison, School of Pharmacy, Faculty of Health Sciences, University of Namibia, Windhoek, Namibia
Lydia Irengeya, School of Pharmacy, Faculty of Health Sciences, University of Namibia, Windhoek, Namibia
Roger K. Verbeeck, School of Pharmacy, Faculty of Health Sciences, University of Namibia, Windhoek, Namibia


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Abstract

Background: Phenytoin and valproic acid, anticonvulsants, have a low therapeutic index and are highly plasma protein bound, mainly to albumin. Hypoalbuminaemia is common in critically ill patients and increases the unbound drug concentration. Thus, monitoring unbound rather than total plasma drug concentrations is recommended to optimise the dosing of these drugs.

Objective: This retrospective study determined unbound plasma concentrations of phenytoin and valproic as a more accurate value of drug levels than total plasma drug concentrations.

Methods: Total plasma concentrations were retrieved for 56 Intensive Care Unit patients for phenytoin and 93 for valproic acid. Total drug concentrations were converted to unbound concentrations using a serum albumin-based normalising equation.

Results: Total phenytoin plasma concentration was below (41.1% of patients), within (46.4%) or above (12.5%) the therapeutic range (10 μg/mL – 20 μg/mL). However, the predicted unbound plasma concentration of phenytoin was above the therapeutic range (1 μg/mL – 2 μg/mL) in the majority of patients (57.1%). For valproic acid, the total plasma concentration of most patients (87.1%) was below the therapeutic range (50 μg/mL – 100 μg/mL); among remaining patients (12.9%), it was within the therapeutic range. In the majority of patients (91.4%), the predicted unbound plasma concentration of valproic acid was between 2.5 μg/mL and 20 μg/mL.

Conclusion: The usefulness of monitoring the total phenytoin or valproic acid levels for dose optimisation is limited as it is an inaccurate indicator of a patient’s drug therapeutic state. Thus, the unbound plasma drug concentrations should be quantified experimentally or predicted in resource-limited settings.


Keywords

phenytoin; valproic acid; critically ill patients; therapeutic drug monitoring; unbound concentration

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