BMC Med Inform Decis Mak - Clinical decision support of therapeutic drug monitoring of phenytoin: measured versus adjusted phenytoin plasma concentrations.


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CKGROUND: Therapeutic drug monitoring of phenytoin by measurement of plasma concentrations is often employed to optimize clinical efficacy while avoiding adverse effects. This is most commonly accomplished by measurement of total phenytoin plasma concentrations. However, total phenytoin levels can be misleading in patients with factors such as low plasma albumin that alter the free (unbound) concentrations of phenytoin. Direct measurement of free phenytoin concentrations in plasma is more costly and time-consuming than determination of total phenytoin concentrations. An alternative to direct measurement of free phenytoin concentrations is use of the Sheiner-Tozer equation to calculate an adjusted phenytoin that corrects for the plasma albumin concentration. Innovative medical informatics tools to identify patients who would benefit from adjusted phenytoin calculations or from laboratory measurement of free phenytoin are needed to improve safety and efficacy of phenytoin pharmacotherapy. The electronic medical record for an academic medical center was searched for the time period from August 1, 1996 to November 30, 2010 for patients who had total phenytoin and free phenytoin determined on the same blood draw, and also a plasma albumin measurement within 7 days of the phenytoin measurements. The measured free phenytoin plasma concentration was used as the gold standard.RESULTS: In this study, the standard Sheiner-Tozer formula for calculating an estimated (adjusted) phenytoin level more frequently underestimates than overestimates the measured free phenytoin relative to the respective therapeutic ranges. Adjusted phenytoin concentrations provided superior classification of patients than total phenytoin measurements, particularly at low albumin concentrations. Albumin plasma concentrations up to 7 days prior to total phenytoin measurements can be used for adjusted phenytoin concentrations.CONCLUSIONS: The results suggest that a measured free phenytoin should be obtained where possible to guide phenytoin dosing. If this is not feasible, then an adjusted phenytoin can supplement a total phenytoin concentration, particularly for patients with low plasma albumin.

Resumo Limpo

ckground therapeut drug monitor phenytoin measur plasma concentr often employ optim clinic efficaci avoid advers effect common accomplish measur total phenytoin plasma concentr howev total phenytoin level can mislead patient factor low plasma albumin alter free unbound concentr phenytoin direct measur free phenytoin concentr plasma cost timeconsum determin total phenytoin concentr altern direct measur free phenytoin concentr use sheinertoz equat calcul adjust phenytoin correct plasma albumin concentr innov medic informat tool identifi patient benefit adjust phenytoin calcul laboratori measur free phenytoin need improv safeti efficaci phenytoin pharmacotherapi electron medic record academ medic center search time period august novemb patient total phenytoin free phenytoin determin blood draw also plasma albumin measur within day phenytoin measur measur free phenytoin plasma concentr use gold standardresult studi standard sheinertoz formula calcul estim adjust phenytoin level frequent underestim overestim measur free phenytoin relat respect therapeut rang adjust phenytoin concentr provid superior classif patient total phenytoin measur particular low albumin concentr albumin plasma concentr day prior total phenytoin measur can use adjust phenytoin concentrationsconclus result suggest measur free phenytoin obtain possibl guid phenytoin dose feasibl adjust phenytoin can supplement total phenytoin concentr particular patient low plasma albumin

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