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.
Highlights
Albendazole is a benzimidazole carbamate drug with anthelmintic and antiprotozoal activity against intestinal and tissue parasites
As there was no interaction between factors nor sex effect, we evaluated the bioequivalence considering all the available data, using a simpler analysis of variance (ANOVA) model that includes the following factors: sequence, subject, type of breakfast, period, and formulation
It is worth noting that the bioavailability of albendazole and its metabolite was much higher when administered after a high-fat breakfast than after a low-fat breakfast, with an increase in Area under the concentration–time curve (AUC) of almost 4 times for albendazole and 2 times for albendazole
Summary
Albendazole is a benzimidazole carbamate drug with anthelmintic and antiprotozoal activity against intestinal and tissue parasites. It is especially indicated for the treatment of systemic helminthic infections such as echinococcosis (hydatid disease) with hepatic, lung or peritoneal cysts, and neurocysticercosis. Albendazole absolute oral bioavailability is less than 5% in humans. After oral administration, it rapidly undergoes first-pass metabolism in the liver. Its plasma half-life (T1/2) is around 9 h It is 70% protein bound (Venkatesan, 1998). A study in human liver microsomes and recombinant cytochrome P450 enzymes (CYP) showed for the first time that albendazole hydroxylation is primarily catalyzed by CYP2J2 (Wu et al, 2013)
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