<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:creator>Tobler A</dc:creator>
  <dc:creator>Hösli R</dc:creator>
  <dc:creator>Mühlebach S</dc:creator>
  <dc:creator>Huber A</dc:creator>
  <dc:date>2016</dc:date>
  <dc:description xmlns:ns0="xml" ns0:lang="en">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, &gt;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 &lt;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.</dc:description>
  <dc:identifier>https://sonar.ch/global/documents/232368</dc:identifier>
  <dc:language>eng</dc:language>
  <dc:relation>info:eu-repo/semantics/altIdentifier/doi/10.1007/s11096-015-0241-x</dc:relation>
  <dc:relation>info:eu-repo/semantics/altIdentifier/pmid/26746902</dc:relation>
  <dc:source>International journal of clinical pharmacy. - 2016</dc:source>
  <dc:subject xmlns:ns1="xml" ns1:lang="en">Phenytoin</dc:subject>
  <dc:subject xmlns:ns2="xml" ns2:lang="en">Serum concentrations</dc:subject>
  <dc:subject xmlns:ns3="xml" ns3:lang="en">Sheiner-Tozer equation</dc:subject>
  <dc:subject xmlns:ns4="xml" ns4:lang="en">Therapeutic Drug Monitoring (TDM)</dc:subject>
  <dc:subject xmlns:ns5="xml" ns5:lang="en">Adolescent</dc:subject>
  <dc:subject xmlns:ns6="xml" ns6:lang="en">Adult</dc:subject>
  <dc:subject xmlns:ns7="xml" ns7:lang="en">Aged</dc:subject>
  <dc:subject xmlns:ns8="xml" ns8:lang="en">Aged, 80 and over</dc:subject>
  <dc:subject xmlns:ns9="xml" ns9:lang="en">Algorithms</dc:subject>
  <dc:subject xmlns:ns10="xml" ns10:lang="en">Anticonvulsants</dc:subject>
  <dc:subject xmlns:ns11="xml" ns11:lang="en">Child</dc:subject>
  <dc:subject xmlns:ns12="xml" ns12:lang="en">Cohort Studies</dc:subject>
  <dc:subject xmlns:ns13="xml" ns13:lang="en">Drug Monitoring</dc:subject>
  <dc:subject xmlns:ns14="xml" ns14:lang="en">Female</dc:subject>
  <dc:subject xmlns:ns15="xml" ns15:lang="en">Humans</dc:subject>
  <dc:subject xmlns:ns16="xml" ns16:lang="en">Male</dc:subject>
  <dc:subject xmlns:ns17="xml" ns17:lang="en">Middle Aged</dc:subject>
  <dc:subject xmlns:ns18="xml" ns18:lang="en">Phenytoin</dc:subject>
  <dc:subject xmlns:ns19="xml" ns19:lang="en">Young Adult</dc:subject>
  <dc:title xmlns:ns20="xml" ns20:lang="en">Free phenytoin assessment in patients: measured versus calculated blood serum levels.</dc:title>
  <dc:type>http://purl.org/coar/resource_type/c_6501</dc:type>
</oai_dc:dc>