PMID- 35836626
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 0972-5229 (Print)
IS  - 1998-359X (Electronic)
IS  - 0972-5229 (Linking)
VI  - 26
IP  - 6
DP  - 2022 Jun
TI  - Estimation of Free Phenytoin Concentration in Critically Ill Patients with 
      Hypoalbuminemia: Direct-measurement vs Traditional Equations.
PG  - 682-687
LID - 10.5005/jp-journals-10071-24235 [doi]
AB  - BACKGROUND: In critically ill patients with low albumin, dose individualization 
      of phenytoin is a challenge. The currently used Sheiner-Tozer equation does not 
      accurately predict the free phenytoin concentration in serum and can result in 
      incorrect dose modifications. The best measure to advocate in these patients is 
      the direct-measurement of free phenytoin concentration. AIMS AND OBJECTIVES: 
      Phenytoin exhibits complex pharmacokinetics, requiring careful therapeutic drug 
      monitoring. This study aimed to compare the accuracy of the established 
      Sheiner-Tozer calculation method against the direct-measurement of free phenytoin 
      concentration in serum by high performance liquid chromatography in critically 
      ill patients with low albumin. MATERIALS AND METHODS: Blood specimens for 
      direct-measurement of both total and free phenytoin concentration were obtained 
      from 57 patients with hypoalbuminemia monitored in the intensive care unit. 
      RESULTS: The median [inter-quartile range (IQR)] for Sheiner-Tozer equation 
      calculated total phenytoin concentration and direct-measured total was 17.14 
      (10.63-24.53) and 9.82 (6.02-13.85) mug mL(-1), respectively. Approximately 53 and 
      5% of patients were found to be subtherapeutic and supratherapeutic for 
      direct-measured total phenytoin concentrations, respectively. In contrast, on 
      applying the Sheiner-Tozer calculation, 23 and 40% had subtherapeutic and 
      supratherapeutic concentrations, respectively, for total phenytoin concentration. 
      The median (IQR) for direct-measured, routine and Sheiner-Tozer equation 
      calculated free phenytoin concentration were 1.92 (1.06-2.76), 0.98 (0.60-1.39), 
      and 1.71 (1.06-2.45) mug mL(-1), respectively. Only 45.7% of patients were in 
      agreement with respect to the therapeutic category when direct-measured free was 
      compared against routine calculation free. CONCLUSION: In patients with low 
      albumin, free phenytoin concentration based on the Sheiner-Tozer corrected 
      equation accurately classified patients based on their therapeutic category of 
      free phenytoin in 73.7% of patients. Hence, for individualization of phenytoin 
      dosage in critically ill patients with low albumin, we recommend 
      direct-measurement of free phenytoin concentration. HOW TO CITE THIS ARTICLE: 
      Wilfred PM, Mathew S, Chacko B, Prabha R, Mathew BS. Estimation of Free Phenytoin 
      Concentration in Critically Ill Patients with Hypoalbuminemia: Direct-measurement 
      vs Traditional Equations. Indian J Crit Care Med 2022;26(6):682-687.
CI  - Copyright (c) 2022; The Author(s).
FAU - Wilfred, Premila M
AU  - Wilfred PM
AUID- ORCID: 0000-0003-0211-2834
AD  - Department of Pharmacology and Clinical Pharmacology, Christian Medical College 
      and Hospital, Vellore, Tamil Nadu, India.
FAU - Mathew, Sumith
AU  - Mathew S
AUID- ORCID: 0000-0002-2993-2392
AD  - Department of Pharmacology and Clinical Pharmacology, Christian Medical College 
      and Hospital, Vellore, Tamil Nadu, India.
FAU - Chacko, Binila
AU  - Chacko B
AUID- ORCID: 0000-0002-1609-2208
AD  - Medical Intensive Care Unit, Christian Medical College and Hospital, Vellore, 
      Tamil Nadu, India.
FAU - Prabha, Ratna
AU  - Prabha R
AUID- ORCID: 0000-0002-0318-9617
AD  - Department of Pharmacology and Clinical Pharmacology, Christian Medical College 
      and Hospital, Vellore, Tamil Nadu, India.
FAU - Mathew, Binu Susan
AU  - Mathew BS
AUID- ORCID: 0000-0001-6532-1559
AD  - Department of Pharmacology and Clinical Pharmacology, Christian Medical College 
      and Hospital, Vellore, Tamil Nadu, India.
LA  - eng
PT  - Journal Article
PL  - India
TA  - Indian J Crit Care Med
JT  - Indian journal of critical care medicine : peer-reviewed, official publication of 
      Indian Society of Critical Care Medicine
JID - 101208863
PMC - PMC9237157
OTO - NOTNLM
OT  - Critical care
OT  - Free phenytoin
OT  - Hypoalbuminemia
OT  - Sheiner-Tozer equation
COIS- Source of support: Nil Conflict of interest: None
EDAT- 2022/07/16 06:00
MHDA- 2022/07/16 06:01
PMCR- 2022/06/01
CRDT- 2022/07/15 02:27
PHST- 2022/07/15 02:27 [entrez]
PHST- 2022/07/16 06:00 [pubmed]
PHST- 2022/07/16 06:01 [medline]
PHST- 2022/06/01 00:00 [pmc-release]
AID - 10.5005/jp-journals-10071-24235 [doi]
PST - ppublish
SO  - Indian J Crit Care Med. 2022 Jun;26(6):682-687. doi: 
      10.5005/jp-journals-10071-24235.