Digoxin is a digitalis glycoside used to treat atrial fibrillation and heart failure. Its effects include increasing the force of heart contractions and slowing ventricular response in atrial fibrillation. Therapeutic drug monitoring is important due to its narrow therapeutic index and interactions with other drugs and conditions affecting absorption, distribution, and elimination. The optimal therapeutic range is 0.8-2 ng/mL, with risks of toxicity above 2.5 ng/mL. Factors like renal impairment, liver disease, hypothyroidism, and hypokalemia can impact digoxin levels and require dosage adjustments.

1. DIGOXIN
Therapeutic drug monitoring

2. Action and uses
• Digoxin is the most widely used of the digitalis glycosides.
• Its primary actions on the heart are those of increasing the force of
contraction and decreasing conduction through the atrioventricular
node.
• Currently, its main role is in the treatment of atrial fibrillation by
slowing down the ventricular response, although it is also used in the
treatment of heart failure in the presence of sinus rhythm.
• The primary method of monitoring its clinical effect in atrial
fibrillation is by measurement of heart rate but knowledge of its phar-macokinetics
can be helpful in predicting a patient's dosage
requirements.

3. Plasma concentration–responserelationship
• <0.5 μcg/L: no clinical effect
• 0.7 μcg/L: some positive inotropic and conduction blocking
effects
• 0.8–2 μcg/L: optimum therapeutic range (0.5–0.9 μcg/L in
patients >65)
• 2–2.5 μcg/L: increased risk of toxicity, although tolerated in
some patients
• >2.5 μcg/L: gastro-intestinal, cardiovascular system and central
nervous system toxicity.

4. absorption
•Digoxin is poorly absorbed from the gastro-intestinal
tract, and dissolution time affects the
overall bioavailability. The two oral formulations
of digoxin have different bioavailabilities:
• F (tablets) =0.65
•F (liquid) =0.8

5. Distribution
• Digoxin is widely distributed and extensively bound in
varying degrees to tissues throughout the body. This results
in a high apparent volume of distribution. Digoxin volume of
distribution can be estimated using the equation 7.3 L/kg
(ideal body weight (BWt)) which is derived from population
data. However, distribution is altered in patients with renal
impairment, and a more accurate estimate in these patients
is given by:
Vd= 3.8 × ideal BWt (3.1 creatinine clearance (mL/min))

6. •A two-compartment model best describes
digoxin disposition, with a distribution time of 6–
8 h. Clinical effects are seen earlier after
intravenous doses, since the myocardium has a
high blood perfusion and affinity for digoxin.
Sampling for TDM must be done no sooner than
6 h post- dose, otherwise an erroneous result
will be obtained.

7. elimination
•Digoxin is eliminated primarily by renal excretion
of unchanged drug (60–80%), but some hepatic
metabolism occurs (20–40%). The population
average value for digoxin clearance is:
digoxin clearance (mL/min) = 0.8 × BWt +
(creatinine clearance (mL/min))

8. •However, patients with severe congestive heart
failure have a reduced hepatic metabolism and a
slight reduction in renal excretion of digoxin:
digoxin clearance (mL/min) = 0.33× BWt
+(0.9 × creatinine clearance (mL/min))
• Ideal body weight should be used in these
equations

9. Practical implications
• Using population averages it is possible to predict plasma
concentrations from specific dosages, particularly since the time to
reach the steady state is long.
• Population values are only averages, and individual values may vary.
In addition, a number of diseases and drugs affect digoxin disposition.
• As can be seen from the preceding discussion, congestive heart
failure, hepatic and renal diseases all decrease the elimination of
digoxin.
• In addition, hypothyroidism increases the plasma concentration
(decreased metabolism and renal excretion) and increases the
sensitivity of the heart to digoxin.

10. Practical implications
• Hyperthyroidism has the opposite effect.
• Hypokalemia, hypercalcaemia, hypomagnesaemia and hypoxia all
increase the sensitivity of the heart to digoxin.
• There are numerous drug interactions reported of varying clinical
significance. The usual cause is either altered absorption or clearance.

11. CLINICAL MONITORING PARAMETERS
•Monitor symptoms of CHF including left sided
failure, pulmonary edema, right sided failure
•As excreted by kidney renal functions should be
monitored 2-3 times
•Serum concentration measurements is also
important in many cases