Population pharmacokinetics of terizidone and cycloserine in patients with drugresistant tuberculosis
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Date
2019
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
University of the Western Cape
Abstract
Introduction: Drug-resistant tuberculosis remains a major world health problem and
one of the leading cause of death worldwide. Despite adequate adherence to antituberculosis
drugs by patients, the emergence of drug-resistance tuberculosis still
occurs. This fact implies other factors leading to the emergence of resistant strains of
Mycobacterium tuberculosis. A multidrug treatment regimen, which may consist of five
to seven different drugs including terizidone, is used in the treatment of drugresistance
tuberculosis. Terizidone is part of the multidrug regimen whose
pharmacokinetics is scarce in literature and plasma concentration profile unknown.
Two molecules of cycloserine joined by terephtalaldehyde moiety makes up a
molecule of terizidone, which is thought to undergo complete metabolism into
cycloserine in vivo. Additionally, the current literature report that terizidone and
cycloserine can be used interchangeably as they are thought to be equivalent. The
aim of this thesis was first to develop and validate bioanalytical methods for
determination of terizidone and cycloserine in patients’ plasma samples. Secondly, to
model population pharmacokinetics of terizidone and cycloserine. Thirdly, to
determine the amount of cycloserine resulting from metabolism of terizidone.
Description
Doctor Pharmaceuticae - DPharm
Keywords
Terizidone, Drug-resistant tuberculosis, Metabolism, Cycloserine, Population pharmacokinetics