Pharmacology

Albendazole Mechanism of Action and Pharmacokinetics: A Closer Look

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Posted By SUMIT SHARMA

Introduction

Have you ever thought about how albendazole works in our body? Today, we will discuss the albendazole mechanism of action (moa) and its pharmacokinetics.

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 generally used for deworming and it is on the list of essential drugs by the WHO (World Health Organisation). 

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

In this post, you will learn how albendazole works and how the body reacts in response to albendazole. 

 

How does albendazole work in the body?

Albendazole works on the genetic material of parasites. Let’s understand the parasite’s genetic structure.

The genetic material of the parasite could be DNA or RNA, which depends on the type of parasite.

Normally, parasites or helminths contain microtubules in the nucleus. These microtubules are fundamental components of parasites.

Microtubules are polymers that are made up of tubulin protein subunits such as alpha and beta tubulin.

These alpha and beta tubulins are monomers. During cell division, alpha and beta subunits get polymerized which converts into dynamic structures called Microtubules

The principal mechanism of action of albendazole is inhibiting polymerization and the cell division process of parasites. 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, which 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, and 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

 

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 acts as a prodrug. 

Suppose you have a neurocysticercosis problem (worms in your brain). In this condition, you need to take albendazole with a fatty meal because you want albendazole in your blood.

When you take albendazole with a fatty meal (approximately 40 g fat), it increases the absorption.

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 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 process. 

 

Where is albendazole absorbed?

Albendazole is a weak base drug. Generally, weak base drugs have good absorption in the basic medium because they remain un-ionized 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 with albendazole because this medicine gets dissolved better with fatty substances.

In the influence of fatty meal, the 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 form. It gets activated after the metabolism of albendazole in the liver. 

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

After albendazole absorption, 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, skin, etc.), where the parasitic worms cause infestation. 

The volume of distribution of ABZ sulfoxide is not very 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 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 be metabolized from lipid-soluble to water-soluble. 

In the 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 conjugated with glucuronide in a Phase 2 reaction that 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 is eliminated quickly. However, the maximum proportion of albendazole sulfone is eliminated via bile. 

Albendazole mechanism of action

 

What is the half-life of albendazole?

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

Suppose you have taken Albendazole tablet 400 mg. It will reach your bloodstream in the form of 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 albendazole dosage depends upon the type and severity of parasitic worms.  As per a study, each person should take albendazole a single dose every six months. 

You must give the albendazole medicine to your kids because they are more at risk of worm infestation. 

To know albendazole dosage, click here

 

Are there any side effects of albendazole?

There are no significant side effects of albendazole in a single-dose therapy. Although, some side effects have been reported as per duration of treatment – 

Common (≥1%) albendazole side effects  

Abdominal pain is most frequently reported during short-dosing of albendazole.

Uncommon (>0.1% and <1%) albendazole side effects

You may also have diarrhoea, nausea, vomiting, dizziness, itchiness and/or skin rashes. 

Rare (< 0.1%) albendazole side effects 

You might have life-threatening side effects but it rarely happens if you are on long-term therapy of albendazole. It could be – 

  • Leukopenia 
  • Aplastic anemia 
  • Pancytopenia 
  • Agranulocytosis 
  • Thrombocytopenia
  • Bone marrow suppression especially in liver disease (such as hepatic echinococcosis) patients 
  • Hypersensitivity reactions including rash, pruritis and urticaria
  • Severe hepatic abnormalities, including jaundice and hepatocellular damage

 

Who should not take albendazole?

Albendazole is contraindicated in certain conditions – 

  • Hypersensitivity to albendazole and other drugs related to benzimidazole derivatives 
  • Liver disease
  • Pregnancy
  • Anemia or any blood disorder like leukopenia

 

Why is albendazole contraindicated in pregnancy?

Albendazole comes in Category C, which is not supposed to be safe in pregnancy.

Drugs in category C carry a risk that cannot be eliminated.

Animal (rat and rabbit) studies have shown that albendazole can cause teratogenic effects (embryotoxicity and skeletal malformations) during pregnancy.

However, studies on pregnant women are not satisfactory.

Therefore, it would be better to stay away from albendazole in pregnancy unless the potential benefit outweighs the potential risk to the fetus.

 

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 does not cause any potential side effects if it is used in one-time administration.

You might need to worry if you have systemic worm infestation.

Suppose you take an albendazole 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 albendazole therapy for tissue parasites, you may also observe a lower blood cell count in your blood test report

In this case, you may require regular blood monitoring during albendazole therapy.

 

What drugs interact with albendazole?

Albendazole does not cause any severe reaction to other drugs. However, 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 antiepileptic 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 

 

Conclusion 

We learned how albendazole works in the body (albendazole mechanism of action) and how your body responds after taking albendazole (pharmacokinetics of albendazole). 

Understanding albendazole’s mechanism of action not only highlights its therapeutic potential but also reinforces its role in global health initiatives aimed at reducing the burden of parasitic infections.

This 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. 

If you found this post 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 a 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 albendazole?

For tissue helminths, albendazole rapidly absorbs in your blood when it is taken with a fatty meal. But for intestinal helminths, you don’t need to take it with a fatty meal. You should take albendazole on an empty stomach, which stays in your intestine and kills the worms. 

Q 4. What is the bioavailability of albendazole?

The bioavailability of albendazole is less than 5%. You cannot get albendazole in your blood because it is a prodrug. The bioavailability of albendazole gets increased if you take it with a fatty meal. It converts into albendazole sulfoxide (active metabolite) in your blood after first-pass metabolism in the liver. 

Q 5. Does albendazole work immediately?

Although the onset of action of albendazole sulfoxide is 2 to 5 hours it typically does not work immediately. Its effectiveness depends on various factors, including the type of parasitic infection being treated, the severity of the infection, and individual patient factors. The effects of albendazole are usually felt three days after taking it.

Sources –

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

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

Albendazole dose for kids in worm infestation – The Miracle Anthelmintic

 

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2 thoughts on “Albendazole Mechanism of Action and Pharmacokinetics: A Closer Look
  1. Yogesh Kumar

    Very nice information sir

  2. Zahra

    thanks. It was very useful information .

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