Assessment of adequacy of loading dose of phenytoin (PTN) in adult intensive care patients using population pharmacokinetics

Putt, M. T., Roberts, J. A., Udy, A. A., Martin, J. H., Jarrett, P., Salmon, N. and Lipman, J. (2010). Assessment of adequacy of loading dose of phenytoin (PTN) in adult intensive care patients using population pharmacokinetics. In: ESICM 2010: Abstracts of Oral Presentations and Poster Sessions, 23rd Annual ESICM Congress. 23rd Annual Meeting of the European Society of Intensive Care Medicine, Barcelona, Spain, (S-413-S-413). 9-13 October 2010. doi:10.1007/s00134-010-2001-7

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Author Putt, M. T.
Roberts, J. A.
Udy, A. A.
Martin, J. H.
Jarrett, P.
Salmon, N.
Lipman, J.
Title of paper Assessment of adequacy of loading dose of phenytoin (PTN) in adult intensive care patients using population pharmacokinetics
Conference name 23rd Annual Meeting of the European Society of Intensive Care Medicine
Conference location Barcelona, Spain
Conference dates 9-13 October 2010
Proceedings title ESICM 2010: Abstracts of Oral Presentations and Poster Sessions, 23rd Annual ESICM Congress   Check publisher's open access policy
Journal name Intensive Care Medicine   Check publisher's open access policy
Place of Publication Heidelberg, Germany
Publisher Springer
Publication Year 2010
Year available 2010
Sub-type Published abstract
DOI 10.1007/s00134-010-2001-7
ISSN 0342-4642
1432-1238
0935-1701
Volume 36
Start page S-413
End page S-413
Total pages 1
Collection year 2011
Language eng
Formatted Abstract/Summary
Introduction: Phenytoin (PTN) is a highly protein bound anticonvulsant agent commonly employed in intensive care. Given the high morbidity associated with uncontrolled seizures in this setting, rapid attainment of therapeutic concentrations is mandated.

Objectives:
To define the population pharmacokinetics (PK) of phenytoin in the critically ill, in addition to risk factors for sub-therapeutic dosing.

Methods:
Free and total PTN concentrations were measured in serum by means of high performance liquid chromatography following microfiltration, two to three times in the first 24 h after a loading dose. Population PK modelling, including intra and interindividual variability, were determined using NONMEM(R).

Results: Fifty three patients (total of 153 plasma samples) where included in the study. Demographic and pharmacokinetic data are presented in table 1. A one compartment linear model adequately described the pharmacokinetics of loading doses of PTN. The mean clearance and volume of distribution for PTN were 0.024 L kg/h and 1.08 L/kg respectively. The loading dose was within recommended guidelines (10–20 mg/kg) for the majority of cases. Protein binding was consistently ~ 90% when albumin levels were[25 mmol/L and hypoalbuminaemia was associated with higher unbound (free) PTN levels. The percentage of free and total trough levels that were therapeutic were 49% and 38% respectively.

Conclusions: This study has developed a population PK model of PTN loading in critically ill patients. Hypoalbuminaemia was shown to be a critical factor in dosing requirements. In approximately 50% of patients, the trough PTN level was below the therapeutic range, suggesting that higher dosing may be required.
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Q-Index Code CX
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Institutional Status UQ
Additional Notes Special Issue: "ESICM 2010: Abstracts of Oral Presentations and Poster Sessions, 23rd Annual ESICM Congress, Barcelona, Spain, 9--13 October 2010". Abstract number 1303.

Document type: Conference Paper
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Created: Sun, 07 Nov 2010, 00:09:43 EST