Fig 1.
PRISMA diagram illustrating the systematic review workflow.
Web of Science and PubMed were searched on 22nd July 2022 using the keywords albendazole AND (treatment* OR dose* OR pharma* OR “half-life” OR “half life”). This produced a total of 6,855 results after duplicate removal, of which 246 were retained for full text screening. A total of 210 of the retained articles were subsequently excluded based on pre-defined exclusion criteria (see Systematic review of albendazole pharmacokinetics literature, in Methods), yielding 36 studies containing temporally disaggregated data on albendazole sulfoxide plasma concentrations following treatment with a single dose of albendazole. These 36 references contained a total of 113 time-series measuring albendazole and/or albendazole sulfoxide blood plasma concentrations over time in different groups.
Fig 2.
Schematic representation of the model describing albendazole and albendazole sulfoxide pharmacokinetics.
A compartmental model consisting of a series of linked ordinary differential equations (ODEs) was developed to simulate the pharmacokinetics of albendazole and its pharmacodynamically-active metabolite, albendazole sulfoxide, in plasma following a single oral dose. (A) Schematic representation illustrating the model structure and the way in which the different compartments are linked. (B) Overview of the ODEs governing the model, representing the amount of albendazole in the gut (G) and concentration of the drug (or its metabolite albendazole sulfoxide) in the liver (L) and systemic circulation, plasma (P). The received dose is further scaled by a systemic availability parameter not shown here (see Text B in S1 File for further details and full description of the model equations).
Fig 3.
Albendazole sulfoxide pharmacokinetic variability, stratified by patient and dosage features.
In all panels displayed above, each pale line represents the fitted model output for a single time-series, with the darker lines representing the average of the time-series for a given category. Factors explored were (A) Sex; (B) Feeding Status (according to whether groups had received the single dose of albendazole alongside a fatty meal or not); (C) Dose (with time-series crudely categorised into high/low strata based on whether the dose was higher or lower than 400 mg); (D) Infection Status (defined, following the article associated with each time-series, as whether the patient group were receiving treatment for a known infection or not); (E) Co-Administered Drugs (i.e. whether albendazole was delivered alone or in tandem with other drugs); and (F) Age Group, defined as to whether the average age of the patients was under 18 years (children) or ≥18 years (adults).
Table 1.
Regression outputs (p-values) relating pharmacokinetic properties to patients’ characteristics.
Inferred parameters from the fitted pharmacokinetic model, specifically the median values of albendazole sulfoxide (AlbSO) systemic availability, albendazole sulfoxide clearance rate, albendazole sulfoxide AUC400 and CMax400 were regressed onto various patient group demographic and treatment metadata.