An old man enters a hospital with myocardial infarction and severe ventricular arrithmia. The antiarrhythmic drug chosen has a narrow therapeutic window. The minimum toxic plasma concentration is 1.5 times a minimum therapeutic plasma concentration. Day half life is 6 hours. It is essential to maintaining the plasma concentration about the minimum therapeutic level to prevent possible lethal arrhythmia. Of the following the most appropriate dosing regimen would be
Correct Answer: Constant intravenous infusion
Description: Ref-Katzung 10/e p40,43,44 When a drug is administered less frequently, it produces marked variation in the plasma concentrations. In this question the drug has a half life of 6 hours. If we repeat the dose at 6 hourly intervals, there will be 100% variation in the plasma concentration. More frequent dosing will minimize the variation between maximum and minimum plasma concentrations. As the margin of safety of this drug (given in the question) is very low (maximum tolerable concentration is only 1.5 times the effective concentration), constant i.v. infusion is the best route.
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