Assessment of Diet-Related Changes on Albendazole Absorption, Systemic Exposure, and Pattern of Urinary Excretion in Treated Human Volunteers

Abstract

Soil-Transmitted-Helminth (STH) infections are a persistent global public health problem. Control strategies for STH have been based on the use of mass drug administration (MDA) mainly targeting pre-school and school-aged-children, although there is increasing interest in expanding treatment to include adults and others through community-wide MDA. Coverage assessment is critical to understanding the real effectiveness of albendazole (ALB) treatment in those MDA programs. The work described here aims to a) evaluate the effect of type of diet (heavy or a light meal) and fasting before ALB treatment on the systemic disposition of ALB and its metabolites in treated human volunteers and, b) to evaluate the potential feasibility of detecting albendazole metabolites in urine. The data reported here demonstrate that the systemic availability of the active ALB-sulphoxide (ALBSO) metabolite was enhanced more than two-fold after food ingestion (both, a heavy or a light meal). ALB dissolution improvement related to the ingestion of food may modify the amount of drug/metabolites reaching the parasite, affecting drug efficacy and the overall success of MDA strategies. The measurement in urine samples of the amino-ALB-sulphone (NHALBSO 2 ) derivative and ALBSO for up to 96 hours suggests that it may be feasible to develop a non-invasive tool to evaluate compliance/adherence to ALB treatment.

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

“…Together, our results also suggest that different factors impact different pharmacokinetic properties of albendazole and albendazole sulfoxide. For example, whilst receipt of a fatty meal was associated with increases to systemic availability, AUC 400 and C Max 400 (in agreement with previous work exploring its effect [ 26 , 29 ]), age was significantly associated with systemic availability, albendazole sulfoxide half-life and C Max 400 , with significant differences observed between adults and children even after controlling for differences in effective dosage due to differences in body weight.…”

“…In keeping with previous work [26,27,34,53,62], consumption of a fatty meal prior to receiving the dose was associated with increased systemic availability of albendazole sulfoxide (concomitantly elevating the AUC and C Max values achieved) [28,29], a phenomenon thought to be attributed to changes in the drug's solubility (previously shown to be the rate-limiting step in albendazole's absorption [15]) when delivered alongside a fatty meal [62]. 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 [24]), we did not observe any statistically significant differences here.…”

“…A total of 36 references containing 113 time-series detailing the concentration of albendazole and/or albendazole sulfoxide in plasma following treatment with a single dose of albendazole were identified [14,[25][26][27][28][29][30]. Forty-four time-series were data for a single individual and 69 time-series described average plasma concentrations through time for a group of individuals (mean group size = 13.4, interquartile range = 6-18), with the data comprising a total number of 967 individuals who had received a single dose of albendazole.…”

“…A number of factors are thought to underlie this pharmacokinetic variation. Several studies have examined the influence of different drivers, including sex [24], co-administered drugs [14,25], delivery of albendazole alongside a fatty meal [26][27][28][29] and infection status [30,31] on the pharmacokinetic profile of albendazole sulfoxide. However, these studies typically only analyse a single factor, and therefore a systematic understanding of the respective comparative impact of different factors on albendazole's (and particularly albendazole sulfoxide's) pharmacokinetics remains outstanding.…”