P. T. Pollak,1 V. Frenkel2; 1University of Calgary, Calgary, AB, Canada, 2Soroka University Medical Center of the Negev, Beer Sheva, Israel
BACKGROUND: The unusual pharmacokinetic profile of amiodarone contributes to frustration with its “unpredictable” toxicity. Loading and maintenance dosing, and timing of monitoring, are often miscalculated for this drug with a 2-month half-life. Teaching medical learners to appreciate the implications of this half-life can help them individualize drug dosing to improve efficacy and minimize adverse effects.
METHODS: A mathematical model was developed based on the population pharmacokinetics of amiodarone showing the dominance of the peripheral compartment and relatively little variation in its typical half-life. All other factors affecting absorption and clearance can be estimated proportionally by their influence on the time it takes to reach a clinical end point.
RESULTS: The model can be represented visually on a nomogram plot for the learner to see the time it takes for a dose change to affect drug exposure. By knowing the drug’s dosing rate and duration it took to produce a desired response, the maintenance dose required to maintain that exposure can be estimated. The nomogram has been well received by learners who come to an appreciation of why arbitrary dosing regimens produce less desirable results than individually calculated doses.
CONCLUSION: The proposed nomogram provides a more rigorous framework for dose estimation than experience-based guessing, and is intrinsically better than any "one-dose-fits all" strategy. It allows teaching of the time frame in which changes in dose cause changes in drug exposure and therefore when clinical monitoring is best timed. The key benefit of the nomogram is to provide an early, more reliable estimate of the patient's optimum long-term amiodarone maintenance dose, without requiring precise knowledge of their individual pharmacokinetic profile.