Albendazole mechanism of action (moa) & pharmacokinetics: crystal clear concepts

Posted On August 13, 2022January 29, 2023

Introduction

Do you want to know the albendazole mechanism of action (moa) and pharmacokinetics in the human body? If yes, then this article is for you.  

We take albendazole medicine for deworming, get relief and forget. Many people have a curiosity to know the fate of the drug.

Albendazole is a miracle drug because it uniquely kills parasitic worms. 

Albendazole medicine is basically used for deworming, and it comes on the essential drugs list of WHO (World Health Organisation). 

Here, I have made an easy guide to understanding albendazole mechanism of action (moa) and pharmacokinetics. 

After reading this post, you will know how albendazole works and how the body reacts in response to albendazole. 

How does albendazole work in the body?

The principal mechanism of action of albendazole is inhibiting polymerization and the cell division process of helminths. But it also depends on the types of parasitic worms – 

Albendazole mechanism of action for intestinal worms 

When you take albendazole, it goes to your small intestine and is directly active against intestinal worms. 

Albendazole strongly binds to the β-tubulin site of worm parasites. As a result, it inhibits the polymerization process that destroys the assembly of the worm’s microtubules. 

In other words, it stops the cell division process. Moreover, albendazole stops egg production and prevents the hatching of existing eggs. 

Albendazole also stops the glucose supply for helminths. 

You don’t need albendazole in your blood circulation for intestinal helminths (such as hookworm, pinworm, roundworm). 

In this condition, you have to take albendazole on an empty stomach so that it can stay for a longer time in your intestine. Albendazole does not absorb on an empty stomach but is rapidly absorbed with a fatty meal.

Albendazole mechanism of action for tissue worms 

Sometimes, parasitic worms penetrate your blood circulation and tissues via intestine to blood or skin to blood. In this condition, Albendazole act as a prodrug. 

Suppose you have a neurocysticercosis problem (worms in your brain) and take albendazole with a fatty meal. 

Firstly, it goes to your stomach and then the small intestine. From the small intestine, albendazole is rapidly absorbed into your hepatic portal circulation via the inferior mesenteric vein. 

As soon as albendazole reaches the liver, it converts into albendazole sulfoxide by First Pass Metabolism. Here, albendazole sulfoxide is a real anthelmintic for systemic worm infections. 

After reaching blood circulation, it easily crosses your blood-brain barrier (BBB) and enters cerebrospinal fluid (CSF) because albendazole is a highly lipid-soluble drug.

In your brain, albendazole get accumulates in higher concentrations. It effectively kills Taenia solium worms that cause neurocysticercosis. 

Here, albendazole binds on the β-tubulin site of Taenia solium worms, inhibiting polymerization and cell division. 

Where is albendazole absorbed?

Albendazole is a weak base drug. Generally, weak base drugs have good absorption in the basic medium because it remains unionized in an alkaline medium. 

So, albendazole is well absorbed in an alkaline medium like the small intestine. Here, it would be best to take a fatty meal because albendazole dissolves better with fatty substances.

In the influence of fatty meal, albendazole drug readily crosses the bilayer lipid membrane of the small intestine and enters the hepatic portal circulation. By this hepatic portal vein, it goes to your liver for first-pass metabolism. 

How is albendazole metabolized?

Albendazole is a prodrug that is inactive and gets activated after ingestion of albendazole in the liver. 

When you take an albendazole tablet or suspension, it is rapidly absorbed with a fatty meal. 

After the absorption of albendazole, it goes to your liver for First Pass Metabolism via the hepatic portal vein.  

Here, albendazole gets rapidly metabolized in the liver and converts into an active metabolite, i.e., albendazole sulfoxide (primary metabolite). 

Albendazole sulfoxide is an active metabolite (anthelmintic action) that produces a therapeutic or pharmacological effect.  

Albendazole sulfoxide (ABZ sulfoxide) is widely distributed in your entire body. It goes to the target site (like the brain, lungs, etc.), where the parasitic worms cause infestation. 

The volume of distribution of ABZ sulfoxide is not much high because albendazole sulfoxide is 70% bound to plasma protein. It means 70% bound drug and 30% unbound drug (free drug).

This 30 % unbound drug goes to your target tissue for an anthelmintic effect. The rest of the bound drug is slowly released from protein binding and provides a therapeutic effect. 

After the therapeutic effect, albendazole sulfoxide re-enters in your blood and goes to the liver for biotransformation. 

Here, albendazole sulfoxide converts from an active metabolite to an inactive one.

The main purpose of the biotransformation (or metabolism) of albendazole sulfoxide is to eliminate the drug from your body. Albendazole sulfoxide can’t excrete itself because it is a lipid-soluble drug.

Therefore, it has to metabolize from lipid-soluble to water-soluble. 

In phase I reaction, albendazole sulfoxide gets destroyed (or breaks down) so that it cannot go back to your tissue. Here, CYP3A4 P450 enzymes help to introduce oxygen atoms in ABZ sulfoxide and decrease its pharmacological effects.

After that, ABZ sulfoxide gets conjugate with glucuronide in Phase 2 reaction and makes the drug super polar (or water-soluble) – Albendazole sulfone. 

Albendazole sulfoxide (primary metabolite or active metabolite or lipid soluble)

↓

Albendazole sulfone (secondary metabolite or inactive metabolite, or water-soluble)

This ABZ sulfone goes to your kidney and eliminates quickly. But the maximum proportion of albendazole sulfone is eliminated via bile. 

What is the half-life of albendazole?

The half-life of albendazole sulfoxide is around 8.5 hours. This means 50% ABZ sulfoxide will start to eliminate from your body every 8.5 hours. 

Suppose you have taken Albendazole 400 tablet. It will reach in your bloodstream in albendazole sulfoxide 400 mg 

ABZ sulfoxide 400 mg (100%)

       ↓8.5 hrs

ABZ sulfoxide 200 mg (50%)

       ↓17 hrs

ABZ sulfoxide 100 mg (25%)

         ↓25.5 hrs

ABZ sulfoxide 50 mg (12.5%)

      ↓34 hrs

ABZ sulfoxide 25 mg (6.25%)

          ↓42.5 hrs

ABZ sulfoxide 12.5 mg (3.125%)

       ↓51 hrs

ABZ sulfoxide 6.25 mg (1.562%)

          ↓59.5 hrs

ABZ sulfoxide 3.125 mg (0.781%)

It takes around 60 hours to wash out albendazole from your body thoroughly.

How often should albendazole be taken?

The dosage of albendazole depends upon the type and severity of parasitic worms. 

As per a study, each person should take albendazole a single dose every six months. 

But the dose of albendazole may differ in tissue and parasitic intestinal worms. Therefore, you should take the albendazole dose in kids and adults under proper medical supervision. 

To know albendazole dosage, click here

Is albendazole safe for humans?

Albendazole is a well-tolerated and safest drug for deworming. Using albendazole improves the health of entire communities, including child nutrition and development. 

Albendazole drug may cause common side effects like headache, nausea, vomiting, and abdominal pain. 

Suppose you take an ABZ drug for systemic worms like hydatid disease and neurocysticercosis. In this case, it may also elevate the level of your liver enzymes as albendazole is metabolized by the liver.

During ABZ therapy for tissue parasites, you may also observe low platelet count (leukopenia) in your blood test report. 

What drugs interact with albendazole?

Albendazole does not cause any severe reaction to other drugs. But some medicines may interfere with the efficacy of albendazole. 

Drugs that decrease the efficacy of albendazole

Your doctor may increase the albendazole dose if you or your children are on antiepileptics drugs like phenytoin, carbamazepine, and phenobarbital. These drugs are enzyme inducers that decrease the efficacy of albendazole by increasing the metabolism of albendazole. 

Drugs that increase the efficacy of albendazole

Some drugs inhibit the metabolism of albendazole. So, your doctor may decrease the dose of albendazole if you or your children are taking the following medicines or foods – 

• Cimetidine 
• Corticosteroids like dexamethasone, 
• Antiparasitic drugs like praziquantel and levamisole 
• Grapefruit (by inhibiting albendazole metabolism)
• Long-term administration of antiretroviral drug – ritonavir 

Who should not take albendazole?

Albendazole may contraindicate in certain conditions – 

• Hypersensitivity to albendazole and other drugs related to benzimidazole derivatives 
• Liver disease
• Pregnancy – cause teratogenicity in animals but lack safety data in human. 
• Anemia or any blood disorder like leukopenia

Conclusion 

Finally, we have seen the albendazole mechanism of action and pharmacokinetics in the human body.

We learned how albendazole works in the body and how your body responds after taking albendazole. 

Albendazole medicine effectively works in intestinal and tissue helminths by binding on the β-tubulin site of worm parasites.

It is the safest anthelmintic with minimal side effects. 

We should especially focus on the administration of albendazole – with food (for tissue parasites) or without food (intraluminal parasites). It is always best to take albendazole under proper medical supervision. 

If you found this post (Albendazole mechanism of action) informative, please share it on social media. 

Have questions? 

Let me know in the comments below. I will try my best to answer all of them.

FAQ

Q 1 How long does albendazole stay in your system?

The half-life of albendazole sulfoxide in your blood is 8.5 hours. So, it effectively works for around 8.5 hours. But it stays in your blood for 2-3 days for complete washout. 

Q 2 What is the mechanism of action of mebendazole?

Since mebendazole also belongs to the benzimidazole class of drugs. So, its mechanism of action is similar to albendazole. Mebendazole is also bound to the β-tubulin site of parasitic worms.

Q 3 What happens after taking albendazoles?

After taking albendazole, it rapidly absorbs in your blood for tissue helminths. But in intestinal helminths, it does not absorb if you have taken it on an empty stomach. It stays in your intestine and kills the worms. 

Sources – 

1. KD Tripathi. Essentials of medical pharmacology, 7^th edition. Jay Pee Brothers, 2013; Anthelmintic drugs, Chapter-61, Pages – 849 to 851.

2. Michelle A. Clark et al. Lippincott’s Illustrated reviews: Pharmacology, 5^th edition. Wolters Kluwer health, 2012. Anthelmintic drugs; Chapter-27; Pages 455 to 460.

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