Severe intoxication after phenytoin infusion: A preventable pharmacogenetic adverse reaction
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To the Editor:
We read with interest the report by Citerio et al.1 describing the genetic profile of a patient with presumed phenytoin (PHT) slow metabolism. We are concerned that the plasma concentration/time data provided by the authors do not support the hypothesis of the patient truly having slow PHT metabolism phenotype. Alternate explanations for these data are more likely.
First, a plasma concentration of 79 mcg/mL within 2 hours of a 15 mg/kg PHT loading dose primarily reflects dose size and volume of distribution, and only minimally reflects rate of metabolism.2 The data presented suggest that the patient had a very small volume of distribution, a laboratory error, or, more likely, that the patient received an incorrect dose of PHT. Second, a patient with a typical PHT metabolic rate would require 8 days for the plasma concentration to drop from 79 to 10 mcg/mL based on data generated from a Bayesian PHT dosing program we have tested extensively.3,4⇓ We entered the patient data (extrapolated from the graph provided) presented by the authors into our modeling program and estimated a Km of 5.8 …
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