We would like to thank Kane 1 for his interest in our article 2 and thoughtful comments. He inquired about our laboratory practice of analyzing phenytoin serum concentrations because phenytoin protein binding capacity may be influenced at temperatures greater than room air, which may necessitate modifying our calculations. Similar to most laboratory practices in US hospitals in analyzing phenytoin serum concentrations, our hospital conducts these processes at room temperature.They also mentioned about the interest of application of our findings to other equations, particularly the traditional and revised Winter-Tozer. We chose to use the traditional Sheiner-Tozer formula because we felt that this is what is typically used in practice and what is taught in training. Interestingly, when we utilized an alternative correction factor (0.29) in our cohort, the correlation did not change (r = 0.817), and agreement with level interpretation was 66% (unpublished data).We agree with the limitations described with the categorizations that were used for level assessment. We choose this method rather than percentage error because as the model for providing clinical pharmacy services is changing, many institutions rely on trigger tools to identify areas for pharmacokinetic interventions. We felt that this method would best reveal the limitations with such a practice as it relates to adjusted phenytoin levels.We both agree that total phenytoin levels cannot be highly reliable in estimating free concentrations in critically ill patients. Furthermore, we recognize that free phenytoin levels may not be readily available at some institutions, which may pose a significant barrier to obtaining real-time data to make clinical decisions. However, increased awareness regarding the limitations with these adjustment equations is needed, as is further research, to identify an accurate surrogate for free phenytoin levels. In all cases, prudent evaluation of clinical response for efficacy and safety is required.
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