Albendazole: Mechanism of Action

How It Works

Albendazole is converted on first-pass to albendazole sulphoxide (active metabolite) then to inactive albendazole sulphone by CYP3A4. Albendazole sulphoxide binds parasite β-tubulin with ~250× greater affinity than mammalian tubulin. Its high lipophilicity enables penetration of the blood-brain barrier (~40% of plasma levels in CSF) and hepatic hydatid cysts — making it uniquely effective for echinococcosis, neurocysticercosis, and toxocariasis. Unlike mebendazole (poorly absorbed, primarily intraluminal action), albendazole sulphoxide achieves therapeutic systemic concentrations. Fatty food increases oral bioavailability 5-fold, critical for tissue-stage infections.

Receptor / Target Profile

• •Parasite β-tubulin — binding affinity 250× higher than mammalian tubulin
• •CYP3A4 — metabolises to active sulphoxide (peak levels 2–5 hours post-dose with fatty meal)
• •P-glycoprotein (intestinal efflux) — limits fasted bioavailability; P-gp inhibitors increase absorption
• •Glucose transporter complex — indirect disruption via cytoskeletal detachment

Pharmacokinetics

Fasted bioavailability ~5%; enhanced 5-fold with fatty food. Extensively protein-bound (>70%). First-pass metabolism to active sulphoxide. WHO dose: 400mg single dose for intestinal helminths; 400mg twice daily × 28-day cycles (with food) for echinococcosis.