Mathematical model and tool to explore shorter multi-drug therapy options for active pulmonary tuberculosis
Standard treatment for active tuberculosis (TB) requires drug treatment with at least four drugs over six months. Shorter-duration therapy would mean less need for strict adherence, and reduced risk of bacterial resistance. A system pharmacology model of TB infection, and drug therapy was developed...
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| Veröffentlicht in: | PLoS computational biology 2020-08, Vol.16 (8), p.e1008107-e1008107 |
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| creator | Fors, John Strydom, Natasha Fox, William S Keizer, Ron J Savic, Radojka M |
| description | Standard treatment for active tuberculosis (TB) requires drug treatment with at least four drugs over six months. Shorter-duration therapy would mean less need for strict adherence, and reduced risk of bacterial resistance. A system pharmacology model of TB infection, and drug therapy was developed and used to simulate the outcome of different drug therapy scenarios. The model incorporated human immune response, granuloma lesions, multi-drug antimicrobial chemotherapy, and bacterial resistance. A dynamic population pharmacokinetic/pharmacodynamic (PK/PD) simulation model including rifampin, isoniazid, pyrazinamide, and ethambutol was developed and parameters aligned with previous experimental data. Population therapy outcomes for simulations were found to be generally consistent with summary results from previous clinical trials, for a range of drug dose and duration scenarios. An online tool developed from this model is released as open source software. The TB simulation tool could support analysis of new therapy options, novel drug types, and combinations, incorporating factors such as patient adherence behavior. |
| doi_str_mv | 10.1371/journal.pcbi.1008107 |
| format | Article |
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Shorter-duration therapy would mean less need for strict adherence, and reduced risk of bacterial resistance. A system pharmacology model of TB infection, and drug therapy was developed and used to simulate the outcome of different drug therapy scenarios. The model incorporated human immune response, granuloma lesions, multi-drug antimicrobial chemotherapy, and bacterial resistance. A dynamic population pharmacokinetic/pharmacodynamic (PK/PD) simulation model including rifampin, isoniazid, pyrazinamide, and ethambutol was developed and parameters aligned with previous experimental data. Population therapy outcomes for simulations were found to be generally consistent with summary results from previous clinical trials, for a range of drug dose and duration scenarios. An online tool developed from this model is released as open source software. The TB simulation tool could support analysis of new therapy options, novel drug types, and combinations, incorporating factors such as patient adherence behavior.</description><identifier>ISSN: 1553-7358</identifier><identifier>ISSN: 1553-734X</identifier><identifier>EISSN: 1553-7358</identifier><identifier>DOI: 10.1371/journal.pcbi.1008107</identifier><identifier>PMID: 32810158</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Antiinfectives and antibacterials ; Bacteria ; Bacterial infections ; Bioengineering ; Biology and Life Sciences ; Chemotherapy ; Clinical trials ; Computer simulation ; Dose-response relationship ; Drug dosages ; Drug resistance ; Drug therapy ; Ethambutol ; Granuloma ; Granulomas ; Immune response ; Immune system ; Immunosuppressive agents ; Infections ; Investigations ; Isoniazid ; Mathematical models ; Medicine and Health Sciences ; Open source software ; Pharmacodynamics ; Pharmacokinetics ; Pharmacology ; Pharmacy ; Pyrazinamide ; Research and Analysis Methods ; Rifampin ; Risk management ; Risk reduction ; RNA polymerase ; Simulation ; Software ; Tuberculosis</subject><ispartof>PLoS computational biology, 2020-08, Vol.16 (8), p.e1008107-e1008107</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Fors et al. 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Shorter-duration therapy would mean less need for strict adherence, and reduced risk of bacterial resistance. A system pharmacology model of TB infection, and drug therapy was developed and used to simulate the outcome of different drug therapy scenarios. The model incorporated human immune response, granuloma lesions, multi-drug antimicrobial chemotherapy, and bacterial resistance. A dynamic population pharmacokinetic/pharmacodynamic (PK/PD) simulation model including rifampin, isoniazid, pyrazinamide, and ethambutol was developed and parameters aligned with previous experimental data. Population therapy outcomes for simulations were found to be generally consistent with summary results from previous clinical trials, for a range of drug dose and duration scenarios. An online tool developed from this model is released as open source software. 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| subjects | Antiinfectives and antibacterials Bacteria Bacterial infections Bioengineering Biology and Life Sciences Chemotherapy Clinical trials Computer simulation Dose-response relationship Drug dosages Drug resistance Drug therapy Ethambutol Granuloma Granulomas Immune response Immune system Immunosuppressive agents Infections Investigations Isoniazid Mathematical models Medicine and Health Sciences Open source software Pharmacodynamics Pharmacokinetics Pharmacology Pharmacy Pyrazinamide Research and Analysis Methods Rifampin Risk management Risk reduction RNA polymerase Simulation Software Tuberculosis |
| title | Mathematical model and tool to explore shorter multi-drug therapy options for active pulmonary tuberculosis |
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