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Free phenytoin assessment in patients: measured versus calculated blood serum levels

Tobler, Andrea and Hösli, Raphael and Mühlebach, Stefan and Huber, Andreas. (2016) Free phenytoin assessment in patients: measured versus calculated blood serum levels. International journal of clinical pharmacy [2210-7703], 38 (2). pp. 303-309.

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Official URL: https://edoc.unibas.ch/72675/

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Abstract

Total serum drug levels are routinely determined for the therapeutic drug monitoring of selected, difficult-to-dose drugs. For some of these drugs, however, knowledge of the free fraction is necessary to adapt correct dosing. Phenytoin, with its non-linear pharmacokinetics, >90 % albumin binding and slow elimination rate, is such a drug requiring individualization in patients, especially if rapid intravenous loading and subsequent dose adaptation is needed. In a prior long-term investigation, we showed the excellent performance of pharmacy-assisted Bayesian forecasting support for optimal dosing in hospitalized patients treated with phenytoin. In a subgroup analysis, we evaluated the suitability of the Sheiner-Tozer algorithm to calculate the free phenytoin fraction in hypoalbuminemic patients.; To test the usefulness of the Sheiner-Tozer algorithm for the correct estimation of the free phenytoin concentrations in hospitalized patients.; A Swiss tertiary care hospital.; Free phenytoin plasma concentration was calculated from total phenytoin concentration in hypoalbuminemic patients and compared with the measured free phenytoin. The patients were separated into a low (35 ≤ albumin ≥ 25 g/L) and a very low group (albumin <25 g/L) for comparing and statistically analyzing the calculated and the measured free phenytoin concentration.; Calculated and the measured free phenytoin concentration.; The calculated (1.2 mg/L (SD = 0.7) and the measured (1.1 mg/L (SD = 0.5) free phenytoin concentration correlated. The mean difference in the low and the very low albumin group was: 0.10 mg/L (SD = 1.4) (n = 11) and 0.13 mg/L (SD = 0.24) (n = 12), respectively. Although the variability of the data could be a bias, no statistically significant difference between the groups was found: t test (p = 0.78), the Passing-Bablok regression, the Spearman's rank correlation coefficient of r = 0.907 and p = 0.00. The Bland-Altman plot including the regression analysis revealed no systematic differences between the calculated and the measured value [M = 0.11 (SD = 0.28)].; In absence of a free phenytoin plasma concentration measurement also in hypoalbuminemic patients, the Sheiner-Tozer algorithm represents a useful tool to assist therapeutic monitoring to calculate or control free phenytoin by using total phenytoin and the albumin concentration.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Klinische Pharmazie/Spitalpharmazie (Meier)
UniBasel Contributors:Mühlebach, Stefan F
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:2210-7711
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:17 May 2020 19:11
Deposited On:17 May 2020 19:11

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