Factors associated with variation in single-dose albendazole pharmacokinetics: A systematic review and modelling analysis
Authors: Whittaker Charles , Chesnais Cédric B. , Pion Sébastien D.S. , Kamgno Joseph , Walker Martin , Basáñez Maria-Gloria , Boussinesq Michel 
Published: May 2022

Background

Albendazole is an orally administered anti-parasitic medication with widespread usage in a variety of both programmatic and clinical contexts. Previous work has shown the drug to be characterised by significant inter-individual pharmacokinetic variation. This variation is thought to have important consequences for treatment success, but current understanding of the factors associated with this variation remains incomplete.

Methodology/Principal Findings

We carried out a systematic review to identify references containing temporally disaggregated data on the blood concentration of albendazole and/or (its pharmacologically-active metabolite) albendazole sulfoxide following a single oral dose. These data were then integrated into a mathematical modelling framework to infer key pharmacokinetic parameters and relate them to characteristics of the populations being treated. These characteristics included age, weight, sex, dosage, infection status, and whether patients had received a fatty meal prior to treatment or other drugs alongside albendazole. Our results highlight a number of factors systematically associated with albendazole pharmacokinetic variation including age, existing parasitic infection and receipt of a fatty meal. These factors impact different aspects of the drug’s pharmacokinetic profile. Whilst age is significantly associated with albendazole sulfoxide half-life, receipt of a fatty meal prior to treatment was associated with increased albendazole bioavailability (and by extension, peak blood concentration and total drug exposure following the dose). Parasitic infection (particularly echinococcosis and neurocysticercosis) was associated with altered pharmacokinetic parameters, with infected populations displaying distinct characteristics to uninfected ones.

Conclusions/Significance

These results highlight the extensive inter-individual variation that characterises albendazole pharmacokinetics and provides insight into some of the factors associated with this variation.

Author Summary

Albendazole is a broad-spectrum anti-parasitic medication widely used in the treatment of a variety of parasitic worm infections. Previous studies have demonstrated significant variation in the pharmacokinetics of albendazole (and its pharmacologically active metabolite albendazole sulfoxide), leading to substantial inter-individual variability in blood plasma concentrations following a dose of the drug being given. This variation is thought to have important consequences for treatment success but our understanding of the factors driving this variation remain incomplete. In this study, we carried out a systematic review to identify references with data on albendazole and albendazole sulfoxide concentrations in the blood following a single oral dose. We then fitted a mathematical model of albendazole pharmacokinetics to these data to infer key pharmacokinetic parameters and relate them to characteristics of the populations being treated. We found that receipt of a fatty meal prior to treatment was associated with increased albendazole bioavailability, that the half-life of albendazole sulfoxide in the blood varied significantly with age, and that both echinococcosis and neurocysticercosis were associated with altered pharmacokinetic profiles compared to healthy individuals. Our work provides insight into some of the factors systematically associated with variation in albendazole pharmacokinetics.