Intravenous phenytoin a retrospective analysis of

Authors: Andrea Tobler Stefan Mühlebach

Publish Date: 2013/06/29

Volume: 35, Issue: 5, Pages: 790-797

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Abstract

Background In the hospital medication management for effective antiepileptic therapy with phenytoin PHT often needs rapid IV loading and subsequent dose adjustment according to therapeutic drug monitoring TDM Objective To investigate PHT performance in reaching therapeutic target serum concentration rapidly and sustainably a Bayesian forecasting BF regimen was compared to conventional dosing CD according to the official summary of product characteristics Setting A 500–600 bed acute care teaching hospital in Switzerland serving as a referral centre for neurology and neurosurgery Method In a retrospective single centre longterm analysis of hospitalized in and outpatients all PHT serum tests from the central hospital laboratory from 1997 to 2007 were assessed The BF regimen consisted of a guided body weightadapted rapid IV PHT loading over 5 days with predefined TDM time points The conventional dosage was performed without written guidance Assuming nonnormally distributed data nonparametric statistical methods for analysis were applied Main outcome measure The extent of target therapeutic PHT serum levels 40–80 μmol/L was measured and compared between the two regimens Also the influence of gender and age was analysed Results A total of 6120 PHT serum levels 2819 BF and 3301 conventionally dosed from 2589 patients 869 BF and 1720 conventionally dosed were evaluated and compared 636  of the PHT serum levels from the BF group were within the therapeutic range compared with only 340  in the conventional group p  00001 The mean BF serum level was 520 ± 221 μmol/L within target range n = 2819 whereas the mean serum level of the CD was 398 ± 282 μmol/L subtarget range n = 3301 In the BF group men had small but significantly lower PHT serum levels compared to women p  00001 The conventionally dosed group showed no significant gender differences p = 0187 A comparative subanalysis of agerelated groups children adolescents adults seniors and elderly showed significantly lower target levels p  00001 for each group in the conventional dosed group compared to BF Conclusion Comparing the two cohorts BF with the welldefined dose regimen showed significantly better performance in reaching therapeutic PHT serum levels rapidly and for longer durationThe authors would like to thank Prof H Landolt MD head of Neurosurgery at the Kantonsspital Aarau Switzerland for his collaboration and contributions to this study and to Prof A Huber MD head of the Central Medicinal Laboratory also at the Kantonsspital Aarau for his support The authors wish to acknowledge the help of PD W Berchtold PhD emeritus from the University of Applied Sciences Northwestern Switzerland in statistical evaluation as well as Prof S Krähenbühl and Prof HJ Huwyler from the Pharmaceutical Department of the University of Basel for critically reviewing this manuscriptThe investigation and the PhD grant was supported by the Kantonsspital Aarau Switzerland Fund for Science and Continuing Education and by the University of Basel thirdparty grant FO119900 for Clinical Pharmacy project on CNS drug kinetics and patient monitoringThe submitting author is a scientific director at Vifor Pharma Ltd Glattbrugg Switzerland and holds an additional appointment at the Medical Faculty and the Dept of Pharmaceutical Sciences at the University of Basel with a professorship in pharmacology and hospital pharmacy Vifor Pharma Ltd is not involved in this investigation and has no pharmaceutical products services or RD related to the topic Their focus is on iron deficiency treatment especially with IV iron preparations

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