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Digoxin is one of the most commonly used drugs in medicine. Despite this widespread use and a history of over 200 years of clinical use and research, much controversy continues concerning its efficacy and safety.
Two of the most prominent features of the clinical use of digoxin are its narrow therapeutic index and an Endpoint of therapy which is difficult to define and measure. Digitalis toxicity is one of the most frequently encountered drug-related causes of hospitalization. Conversely, the effect of serum digoxin concentrations below 0.8 ng/ml is clinically unimportant in most patients.
The great variability in serum digoxin concentrations in patients given the same dose has led to the development of nomograms and equations designed to estimate the optimal digoxin dosage. These methods include factors such as age, weight, sex, renal function, disease state, and concurrent drug therapy to calculate the dose and corresponding serum concentration. An accurate method could decrease the potential for drug toxicity, which can be life-threatening, and decrease the time period required to optimize therapy, which is otherwise done by trial and error.
Lalonde and Pao compared the accuracy of eighteen different digoxin dosing methods. The method of Dobbs and Koup as modified by Koda-Kimble, appeared to produce the best balance of minimum bias and greatest precision. Using a target concentration of 1.2 ng/ml, the Koda-Kimble method achieves a concentration between 0.9 and 1.5 ng/ml in 80% of cases. However, some patients will have measured serum digoxin concentrations well outside this range.
An adequate loading dose is necessary for rapid attainment of therapeutic serum levels. Choosing to initiate therapy with out a loading dose means that, because of digoxin's long half-life, therapeutic serum levels may not be achieved for weeks.