Chemical Structure
The digitoxin molecule has a complex steroid structure. Its core consists of a cyclopentanoperhydrophenanthrene ring attached to a lactone ring and a sugar moiety. The drug consists of an aglycone and three molecules of digitoxose.
The main structural difference between digitoxin and the more modern digoxin is the absence of an additional hydroxyl group (-OH) at the C12 position of the steroid nucleus. This exact chemical feature makes digitoxin a lipophilic, non-polar compound, fundamentally altering its fate in the body.
Unique Pharmacokinetics
The lipophilicity of digitoxin determines its pharmacokinetic profile, which must be memorized for medical exams:
- Absorption: Virtually complete from the GI tract. Bioavailability reaches 95–100%.
- Plasma protein binding: Very high (90–97%), creating a drug depot in the blood.
- Metabolism: Occurs in the liver via microsomal oxidation. Digitoxin acts as a substrate for aliphatic hydroxylation involving endoplasmic reticulum enzymes (primarily cytochrome P-450).
- Enterohepatic recirculation: This is a crucial mechanism for the drug's prolonged retention in the body. Digitoxin is partially excreted via bile into the intestine, where it is reabsorbed and returned to the liver, forming a closed circulation loop.
- Excretion: Metabolites are excreted via the kidneys.
The elimination half-life ($t_{1/2}$) is exceptionally long, ranging from 4 to 7 days.
Indications and Temporal Parameters
The drug is indicated for chronic heart failure and supraventricular tachyarrhythmias.
When administered orally, pharmacodynamics unfold extremely slowly:
- Latent period: 2–4 hours.
- Peak effect: Achieved only after 8–12 hours.
- Duration of action: After a single dose, effects persist for 14 to 21 days.
Safety Profile and Accumulation
Digitoxin exhibits the most pronounced material accumulation capacity among all cardiac glycosides. This is a direct consequence of its pharmacokinetics: slow hepatic metabolism, strong protein binding, and enterohepatic recirculation.
Consequently, the risk of severe intoxication is significantly higher than with other drugs in this class. In modern clinical practice, digitoxin is rarely used and is not included in the primary list of active cardiac glycosides (unlike digoxin, lanatoside C, or ouabain).
Biological Standardization
Because digitoxin is of plant origin, its potency requires strict standardization. Plant raw materials contain enzymes capable of converting primary ("genuine") glycosides into secondary ones, causing potency to vary significantly between batches.
Potency assessment is performed by comparing the test sample activity against a standard reference. The primary unit of measurement is the Frog Unit of Activity (FUA). This is the minimum dose required to cause systolic cardiac arrest in a majority of test frogs (cat and pigeon units are used less frequently).
For comparison: 1 g of foxglove leaves contains 50–66 FUAs, whereas 1 g of pure digitoxin has an activity of 8,000–10,000 FUAs.
Dosage Forms and Administration
According to prescription references, Digitoxinum is administered in two forms:
- Oral: Tablets of 0.1 mg (single dose 0.1 mg).
- Rectal: Suppositories of 0.15 mg (single dose 0.15 mg).