Abstract
The unpalatability of antituberculosis drugs is often cited as a major cause of non-adherence in children, yet limited quantitative taste assessment data are available. The aim of this research was to quantify the bitterness of isoniazid, rifampicin, pyrazinamide, and ethambutol dihydrochloride using two in vivo (a human taste panel and a rat brief-access taste aversion (BATA) model) and one in vitro (sensor) method. The response of the Insent TS-5000Z electronic tongue was compared to the in vivo drug concentration found to elicit and suppress half the maximum taste response (EC50 in human and IC50 in rats). Using dose-relevant concentrations, an overarching rank order of bitterness was derived (rifampicin > ethambutol > pyrazinamid~isoniazid). In vitro, only ethambutol exhibited a linear response for all sensors/concentrations. Based on the EC50/IC50 generated, a ‘taste index’ was proposed to allow for anticipation of the likelihood of taste issues in practice, taking in account the saturability in the saliva and therapeutic doses; ethambutol and isoniazid were found to be the worst tasting using this measure. The study presents the first quantitative taste analysis of these life-saving drugs and has allowed for a comparison of three methods of obtaining such data. Such information allows the operator to identify and prioritise the drugs requiring taste masking to produce palatable formulations.
Highlights
Tuberculosis is a major global health problem, ranking alongside HIV as a leading cause of mortality worldwide
7 of water concentrations of ethambutol dihydrochloride were deemed significantly different from and each other by the four sensors (p < 0.05); a clear linear dose response was seen for each sensor
The percentage ionised of each group with the lipid membrane of the sensors facilitated, eliciting clear dose was calculated at thesewas pH values and was found to be a for each group at all concentrations
Summary
Tuberculosis is a major global health problem, ranking alongside HIV as a leading cause of mortality worldwide. There are many reasons for non-adherence to tuberculosis treatment, including the complex and onerous nature of this treatment regimen, an inability to meet the financial burden of treatment, and an inability to complete treatment due to side effects [3] Another common reason for non-adherence, in paediatric patients, is the refusal to take medicine due to the unpalatability of formulations [4]. There is, a compelling case for the development of age-appropriate formulations for these drugs; this in turn requires, or would at the very least be facilitated by, a quantitative assessment of the taste of these four frontline drugs that can subsequently be used to assess the taste masking challenges Despite this recognition, there are a paucity of quantitative data available regarding the bitterness levels of these drugs; this represents a major omission in the knowledge base for tuberculosis treatment and an impediment to the development of paediatric formulations
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