Journal article
Free phenytoin assessment in patients: measured versus calculated blood serum levels.
- Tobler A Division of Clinical Pharmacy and Epidemiology and Hospital Pharmacy, University of Basel, Spitalstrasse 26, 4031, Basel, Switzerland.
- Hösli R Division of Clinical Pharmacy and Epidemiology and Hospital Pharmacy, University of Basel, Spitalstrasse 26, 4031, Basel, Switzerland.
- Mühlebach S Division of Clinical Pharmacy and Epidemiology and Hospital Pharmacy, University of Basel, Spitalstrasse 26, 4031, Basel, Switzerland. stefan.muehlebach@unibas.ch.
- Huber A Kantonsspital Aarau, Tellstrasse 25, 5001, Aarau, Switzerland.
- 2016-01-10
Published in:
- International journal of clinical pharmacy. - 2016
Phenytoin
Serum concentrations
Sheiner-Tozer equation
Therapeutic Drug Monitoring (TDM)
Adolescent
Adult
Aged
Aged, 80 and over
Algorithms
Anticonvulsants
Child
Cohort Studies
Drug Monitoring
Female
Humans
Male
Middle Aged
Phenytoin
Young Adult
English
BACKGROUND
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.
OBJECTIVE
To test the usefulness of the Sheiner-Tozer algorithm for the correct estimation of the free phenytoin concentrations in hospitalized patients.
SETTING
A Swiss tertiary care hospital.
METHOD
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.
MAIN OUTCOME MEASURES
Calculated and the measured free phenytoin concentration.
RESULTS
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)].
CONCLUSION
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.
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.
OBJECTIVE
To test the usefulness of the Sheiner-Tozer algorithm for the correct estimation of the free phenytoin concentrations in hospitalized patients.
SETTING
A Swiss tertiary care hospital.
METHOD
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.
MAIN OUTCOME MEASURES
Calculated and the measured free phenytoin concentration.
RESULTS
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)].
CONCLUSION
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.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1007/s11096-015-0241-x
- PMID 26746902
- Persistent URL
- https://sonar.ch/global/documents/232368
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