Fenbendazole Absorption and Bioavailability Explained

Fenbendazole is a benzimidazole antiparasitic drug which has an incomplete understanding regarding how it is processed and eliminated by the body. One of the reasons is bioavailability.

In veterinary medicine, there is a high amount of research regarding the bioavailability of fenbendazole in different animal species when considering the parameters of formulations and food intake. Analyzing the data available will provide better insight for clinicians to explain the large variation in drug exposure when dealing with different animal patients.

What is Fenbendazole Absorption?

For any drug to have a pharmacological effect, it must be absorbed in the body after administration. For fenbendazole, this means dissolving and crossing the intestinal membrane to penetrate the blood circulation. The drug absorption will depend on the drug molecule and the prevailing conditions in the gastrointestinal tract.

According to Merck Veterinary Manual, several factors affect the absorption of drugs by the gastrointestinal tract which includes the rate with which the drug comes into contact with the gastrointestinal walls, motility, as well as the pH and the surface area in the tract.

For fenbendazole, bioavailability will largely depend on the rate of dissolution and absorption in the gut because of its relatively poor water solubility. Consequently, a large amount of fenbendazole could be lost before being absorbed.

What Does Bioavailability Mean?

Bioavailability describes the amount of a given drug which reaches the blood circulation after administration. For many oral drugs, the bioavailability is impacted by the absorption, as well as the changes which occur in the blood due to the first pass effect.

There are two important pharmacokinetic parameters which describe a drug, the first being the maximum concentration (Cmax), and the time taken for the drug to reach its highest concentration (Tmax). The area under the concentration versus time curve (AUC) is the third important pharmacokinetic parameter, and it describes the total drug exposure.

Researchers use this information to better understand how a particular formulation, diet, or dosing regimen impacts fenbendazole exposure.

Does Food Affect Fenbendazole Absorption?

For some animal studies, absorption of fenbendazole is impacted by food.

One study involving 6 beagle dogs investigated administering fenbendazole with an empty stomach and administering with food. Research showed administration with food increased bioavailability, while administration of fenbendazole with food with varying fat content displayed no considerable change in relative bioavailability.

From this, we can assume that in this particular case, the presence of food is more important than the fat content of food.

Another study showed that administration of fenbendazole with feed resulted in increased apparent bioavailability when compared to administration in capsule form.

The effects noted in this study and the other studies mentioned should not be extrapolated to humans.

Does a Higher Dose Mean More Absorption?

Increasing a dose does not necessarily increase absorption.

In one study involving beagle dogs, a dose from 2.5 to 80 mg/kg did not increase absorption.

Another study that looked at dogs showed that a dose from 20 to 100 mg/kg did not increase absorption.

This exemplifies a principle in pharmacokinetics: increasing a dose does not always increase the concentration in the blood.

What Happens After Absorption?

After absorption, fenbendazole goes through distribution and metabolism. Metabolites can also be considered part of the total exposure.

Third-pass metabolites of fenbendazole such as oxfendazole are measured during pharmacokinetic studies. Metabolism also plays a part in how much of an anthelmintic is eventually active in the system. According to Merck Veterinary Manual, first-pass metabolism affects systemic exposure to orally administered anthelmintics.

Fenbendazole and its sulfoxide metabolite can also be measured in the case of an oral dose for dogs. The concentrations of both were found to be measurable after an oral administration. In one study, concentrations were shown to have peak levels many hours after an oral dose.

Does Formulation Affect Bioavailability?

In this case, yes. Bioavailability is also impacted by the physical characteristics of the dosage.

Formulation of an administration dosage of a newer fenbendazole for dogs showed that the new formulation impacts the behavior of the drug and shows measurable systemic exposure after an oral dose.

If exposures of one formulation of fenbendazole are known, one cannot automatically assume the same will hold true for all of the other formulations of fenbendazole. The different tablets, suspensions, and capsules will each behave differently.

Can Bioavailability be Different Between Species?

Yes, it can.

In pigs, fenbendazole was found to have a bioavailability of 27.1%. Oxfendazole was found to be one of the major plasma metabolites of this drug.

In another study, the plasma concentrations of fenbendazole, oxfendazole, and albendazole in dogs were compared. The differences were found to be significant.

Because of the differences in digestive systems, pharmacokinetics are not comparable in dogs and pigs. The same could be said of horses, cattle, and humans.

Can Repeated Doses Change Drug Exposure?

Yes, constant dosing can prolong the exposure time.

In a study of dogs, concentrations of fenbendazole in the plasma were shown to be sustained when the dosing regimen was increased to five days of dosing.

This does not mean that repeated dosing is appropriate for every animal or condition. Treatment schedules must consider veterinary prescribing information and professional guidance.

Fenbendazole Absorption in Humans

Since there is limited published clinical data on fenbendazole, the majority of the available information was obtained from animal research. Although there is not sufficient published clinical evidence on dogs or other animals, we cannot assume that absorption, bioavailability, metabolism or the correct dosing for humans will be as it is for other animals.

Fenbendazole is primarily a veterinary drug, so animal research should not form the basis of an unapproved human dosing regimen.

Final Thoughts

The absorption and bioavailability of fenbendazole is dependent on many factors, including type of food and formulation, dose, the species involved, the prevailing conditions of the gastrointestinal tract, and metabolism. From animal research, fenbendazole may be formulated with food, as it has shown to increase bioavailability, and increasing the dose may not necessarily increase systemic exposure.

Because the majority of the published research is animal research, these findings should be interpreted with caution when considering fenbendazole in humans. More research is required for human pharmacokinetic studies to understand how fenbendazole is absorbed and processed in humans.