High-Fat Breakfast Increases Bioavailability of Albendazole Compared to Low-Fat Breakfast: Single-Dose Study in Healthy Subjects

Abstract

Purpose: Albendazole is a benzimidazole carbamate drug with anthelmintic and antiprotozoal activity against intestinal and tissue parasites. It has been described that the administration with meals increases albendazole absorption. Our aim was to compare the systemic exposure in healthy volunteers of two albendazole formulations after a single oral dose under fed conditions and to evaluate the effect of breakfast composition on albendazole and albendazole sulfoxide bioavailability.Methods: 12 healthy volunteers were included in a 4-period, 4-sequence, crossover, open, randomized, bioequivalence clinical trial, including two stages to compare two formulations of albendazole. Single oral doses of 400 mg albendazole were administered under fed conditions (a low-fat breakfast in first stage and a high-fat breakfast in the second) separated by 7-day washout periods. Plasma albendazole and albendazole sulfoxide concentrations were measured by HPLC-MS/MS.Findings: Albendazole absorption was clearly influenced by the meal composition. A high-fat breakfast increased albendazole and albendazole sulfoxide area under the concentration–time curve (AUC) and maximum concentration (Cmax) by double, compared to a low-fat breakfast. The bioavailability of the two formulations was very similar, although the sample size was not sufficient to demonstrate bioequivalence because the intraindividual variability of albendazole was approximately 60%.Implications: The higher albendazole and albendazole sulfoxide levels when administered with a high-fat meal could be of importance in clinical practice. Since albendazole labeling recommends its administration with meals, it is necessary to insist on taking it with a fatty meal so that the effectiveness of albendazole is not compromised.

Factors associated with variation in single-dose albendazole pharmacokinetics: A systematic review and modelling analysis

“…In-keeping with previous work [22,23,32–34], consumption of a fatty meal prior to receiving the dose was associated with increased bioavailability of albendazole, increasing the amount absorbed into the body (and concomitantly elevating the AUC and C Max values achieved), a phenomenon thought to be attributed to changes in the drug’s solubility (previously shown to be the rate-limiting step in albendazole’s bioavailablity and absorption [27]) when delivered alongside a fatty meal [34]. Whilst prior results from the literature have suggested (modest) differences between men and women in albendazole’s pharmacokinetics (specifically with regards to the AUC and C Max [19]), we did not observe any statistically significant differences here.…”

Pharmacokinetics of menbutone after intravenous and intramuscular administration to sheep

“…Menbutone would act in a similar way as a fatty meal in healthy human subjects. In this way, Ochoa et al ( 17 ) reported an increase in the oral bioavailability of albendazole due to a higher dissolution of this drug in the gastrointestinal tract by stimulating bile secretion.…”

Improvement of Albendazole Bioavailability with Menbutone Administration in Sheep

“…MEN could participate in the mechanisms proposed. More recently, Ochoa et al [ 28 ] reported that a fatty meal enhances ABZ oral bioavailability in healthy human subjects, attributing this higher absorption to food-induced stimulation of bile secretion, increasing the drug solubility.…”

“…Previous studies have shown that the surfactant effect of the bile salts may be related to a higher dissolution of ABZ in the gastrointestinal tract and, consequently, to an increased absorption of this drug [ 27 , 28 , 29 ]. Solubility, but not absorption, was the rate limiting step in the bioavailability of this anthelmintic [ 30 , 31 ].…”