Magister Pharmaceuticae - MPharm / Terizidone (TZD) is considered an essential anti-tuberculosis drug and in South Africa it is prescribed as part of the multi-drug resistant tuberculosis (MDR-TB) treatment regimen. From a literature study it became apparent that very little is known in terms of the physicochemical characteristics of TZD and only one literature source mentions one polymorphic form of this drug. Furthermore, it exhibits neurotoxicity as an adverse effect, leading to the concomitant administration of pyridoxine (PDX) to counteract the TZD-induced side effects. MDR-TB patients experience major side effects from taking the drug for a long period (18 months) and it often results in resistance and poor adherence. This study therefore focused on the possibility to combine TZD and PDX either as co-crystals or as co-amorphous solid-state forms. In order to achieve this a complete physicochemical profile of TZD was determined, since very limited information could be found in literature.

Doctor Pharmaceuticae - DPharm / 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.