Factors associated with variation in single-dose albendazole pharmacokinetics: a systematic review and modelling analysis
File(s)
Author(s)
Type
Journal Article
Abstract
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 that the drug’s pharmacologically active metabolite, albendazole sulfoxide, is characterised by substantial inter-individual pharmacokinetic variation. This variation might have implications for the efficacy of albendazole treatment, 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 plasma 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 albendazole sulfoxide pharmacokinetic parameters and relate them to characteristics of the groups 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 sulfoxide pharmacokinetic variation including age, existing parasitic infection and receipt of a fatty meal. Age was significantly associated with variation in albendazole sulfoxide systemic availability and peak plasma concentration achieved; as well as the clearance rate (related to the half-life) after adjusting for variation in dosage due to differences in body weight between children and adults. Receipt of a fatty meal prior to treatment was associated with increased albendazole sulfoxide systemic availability (and by extension, peak plasma concentration and total albendazole sulfoxide exposure following the dose). Parasitic infection (particularly echinococcosis) 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 sulfoxide pharmacokinetics and provide insight into some of the factors associated with this variation.
Albendazole is an orally administered anti-parasitic medication with widespread usage in a variety of both programmatic and clinical contexts. Previous work has shown that the drug’s pharmacologically active metabolite, albendazole sulfoxide, is characterised by substantial inter-individual pharmacokinetic variation. This variation might have implications for the efficacy of albendazole treatment, 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 plasma 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 albendazole sulfoxide pharmacokinetic parameters and relate them to characteristics of the groups 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 sulfoxide pharmacokinetic variation including age, existing parasitic infection and receipt of a fatty meal. Age was significantly associated with variation in albendazole sulfoxide systemic availability and peak plasma concentration achieved; as well as the clearance rate (related to the half-life) after adjusting for variation in dosage due to differences in body weight between children and adults. Receipt of a fatty meal prior to treatment was associated with increased albendazole sulfoxide systemic availability (and by extension, peak plasma concentration and total albendazole sulfoxide exposure following the dose). Parasitic infection (particularly echinococcosis) 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 sulfoxide pharmacokinetics and provide insight into some of the factors associated with this variation.
Editor(s)
Poonawala, Husain
Date Issued
2022-10-01
Date Acceptance
2022-10-10
Citation
PLoS Neglected Tropical Diseases, 2022, 16 (10)
ISSN
1935-2727
Publisher
Public Library of Science (PLoS)
Journal / Book Title
PLoS Neglected Tropical Diseases
Volume
16
Issue
10
Copyright Statement
Copyright: © 2022 Whittaker et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/36306320
PII: PNTD-D-22-00636
Subjects
BIOAVAILABILITY
DEPENDENT PHARMACOKINETICS
DIETHYLCARBAMAZINE
DRUG-INTERACTIONS
ECHINOCOCCOSIS
EFFICACY
HUMAN PLASMA
Infectious Diseases
IVERMECTIN
Life Sciences & Biomedicine
METABOLITES
Parasitology
SAFETY
Science & Technology
Tropical Medicine
Publication Status
Published
Coverage Spatial
United States
Article Number
e0010497
Date Publish Online
2022-10-28