{"id":{"repo_id":"cape-town","oai_identifier":"oai:open.uct.ac.za:11427/20425"},"canonical_url":"https://search.dev.ndltd.org/etd/cape-town/oai:open.uct.ac.za:11427/20425","repository":{"repo_id":"cape-town","name":"University of Cape Town","base_url":"https://open.uct.ac.za/oai/request"},"display":{"title":"Characterizing population pharmacokinetic/pharmacodynamic relationships in pulmonary tuberculosis infected adults using nonlinear mixed effects modelling","abstract":"This pharmacokinetic sub-study was nested within the phase-III OFLOTUB study investigating the shortening of tuberculosis treatment. A total of 343 adults enrolled in Benin, Guinea, Senegal, and South Africa were randomized to receive rifampicin, isoniazid, pyrazinamide, and ethambutol in the standard 6-month control regimen or the 4-month test regimen where gatifloxacin replaced ethambutol. The pharmacokinetics of all drugs was described at first dose and steady-state using nonlinear mixed-effects modelling, and individual exposures were summarised as area under the concentration-time curve (AUC0-24) and peak concentration. Autoinduction of rifampicin metabolism was characterized with a semi-mechanistic enzyme turn-over model. Gatifloxacin dose was evaluated using Monte Carlo simulations. Lastly, Classification & Regression Tree (CART) analysis techniques were used to identify factors predictive of 2-month culture conversion or 24-month long-term composite outcome. Consistent with literature findings, approximately 73.0, 43.0, 0.3, 6.0 and 0.0% of patients failed to achieve previously reported target concentrations for rifampicin, isoniazid, pyrazinamide, ethambutol, and gatifloxacin, respectively.","abstract_html":"This pharmacokinetic sub-study was nested within the phase-III OFLOTUB study investigating the shortening of tuberculosis treatment. A total of 343 adults enrolled in Benin, Guinea, Senegal, and South Africa were randomized to receive rifampicin, isoniazid, pyrazinamide, and ethambutol in the standard 6-month control regimen or the 4-month test regimen where gatifloxacin replaced ethambutol. The pharmacokinetics of all drugs was described at first dose and steady-state using nonlinear mixed-effects modelling, and individual exposures were summarised as area under the concentration-time curve (AUC0-24) and peak concentration. Autoinduction of rifampicin metabolism was characterized with a semi-mechanistic enzyme turn-over model. Gatifloxacin dose was evaluated using Monte Carlo simulations. Lastly, Classification & Regression Tree (CART) analysis techniques were used to identify factors predictive of 2-month culture conversion or 24-month long-term composite outcome. Consistent with literature findings, approximately 73.0, 43.0, 0.3, 6.0 and 0.0% of patients failed to achieve previously reported target concentrations for rifampicin, isoniazid, pyrazinamide, ethambutol, and gatifloxacin, respectively.","abstract_has_math":false,"creators":["Smythe, Wynand Anton"],"institution":"Division of Clinical Pharmacology","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["McIlleron, Helen","Denti, Paolo"],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016","date_published":"2016","updated_at":"2026-07-22T22:23:36Z","subjects":[],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/11427/20425","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["McIlleron, Helen","Denti, Paolo"]},{"key":"dc:creator","label":"Author","values":["Smythe, Wynand Anton"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2016-07-18T12:51:31Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2016-07-18T12:51:31Z"]},{"key":"dc:date.issued","label":"Date","values":["2016"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Division of Clinical Pharmacology"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Cape Town"]},{"key":"dc:type","label":"Dc Type","values":["Doctoral Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["PhD"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/11427/20425"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["This pharmacokinetic sub-study was nested within the phase-III OFLOTUB study investigating the shortening of tuberculosis treatment. A total of 343 adults enrolled in Benin, Guinea, Senegal, and South Africa were randomized to receive rifampicin, isoniazid, pyrazinamide, and ethambutol in the standard 6-month control regimen or the 4-month test regimen where gatifloxacin replaced ethambutol. The pharmacokinetics of all drugs was described at first dose and steady-state using nonlinear mixed-effects modelling, and individual exposures were summarised as area under the concentration-time curve (AUC0-24) and peak concentration. Autoinduction of rifampicin metabolism was characterized with a semi-mechanistic enzyme turn-over model. Gatifloxacin dose was evaluated using Monte Carlo simulations. Lastly, Classification & Regression Tree (CART) analysis techniques were used to identify factors predictive of 2-month culture conversion or 24-month long-term composite outcome. Consistent with literature findings, approximately 73.0, 43.0, 0.3, 6.0 and 0.0% of patients failed to achieve previously reported target concentrations for rifampicin, isoniazid, pyrazinamide, ethambutol, and gatifloxacin, respectively."]},{"key":"dc:title","label":"Title","values":["Characterizing population pharmacokinetic/pharmacodynamic relationships in pulmonary tuberculosis infected adults using nonlinear mixed effects modelling"]}]}],"canonical_facts":{"dc:contributor.advisor":["McIlleron, Helen","Denti, Paolo"],"dc:creator":["Smythe, Wynand Anton"],"dc:date.accessioned":["2016-07-18T12:51:31Z"],"dc:date.available":["2016-07-18T12:51:31Z"],"dc:date.issued":["2016"],"dc:description.abstract":["This pharmacokinetic sub-study was nested within the phase-III OFLOTUB study investigating the shortening of tuberculosis treatment. A total of 343 adults enrolled in Benin, Guinea, Senegal, and South Africa were randomized to receive rifampicin, isoniazid, pyrazinamide, and ethambutol in the standard 6-month control regimen or the 4-month test regimen where gatifloxacin replaced ethambutol. The pharmacokinetics of all drugs was described at first dose and steady-state using nonlinear mixed-effects modelling, and individual exposures were summarised as area under the concentration-time curve (AUC0-24) and peak concentration. Autoinduction of rifampicin metabolism was characterized with a semi-mechanistic enzyme turn-over model. Gatifloxacin dose was evaluated using Monte Carlo simulations. Lastly, Classification & Regression Tree (CART) analysis techniques were used to identify factors predictive of 2-month culture conversion or 24-month long-term composite outcome. Consistent with literature findings, approximately 73.0, 43.0, 0.3, 6.0 and 0.0% of patients failed to achieve previously reported target concentrations for rifampicin, isoniazid, pyrazinamide, ethambutol, and gatifloxacin, respectively."],"dc:identifier.uri":["http://hdl.handle.net/11427/20425"],"dc:language.iso":["eng"],"dc:publisher.department":["Division of Clinical Pharmacology"],"dc:publisher.institution":["University of Cape Town"],"dc:title":["Characterizing population pharmacokinetic/pharmacodynamic relationships in pulmonary tuberculosis infected adults using nonlinear mixed effects modelling"],"dc:type":["Doctoral Thesis"],"dc:type.qualificationlevel":["Doctoral"],"dc:type.qualificationname":["PhD"]},"updated_at":"2026-07-22T22:23:36Z"}