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Dierig, A., Hoelscher, M., Schultz, S., Hoffmann, L., Jarchow-MacDonald, A., Svensson, E., . . . Heinrich, N. (2023). A phase IIb, open-label, randomized controlled dose ranging multi-centre trial to evaluate the safety, tolerability, pharmacokinetics and exposure-response relationship of different doses of delpazolid in combination with bedaquiline delamanid moxifloxacin in adult subjects with newly diagnosed, uncomplicated, smear-positive, drug-sensitive pulmonary tuberculosis. Trials, 24(1), Article ID 382.
Öppna denna publikation i ny flik eller fönster >>A phase IIb, open-label, randomized controlled dose ranging multi-centre trial to evaluate the safety, tolerability, pharmacokinetics and exposure-response relationship of different doses of delpazolid in combination with bedaquiline delamanid moxifloxacin in adult subjects with newly diagnosed, uncomplicated, smear-positive, drug-sensitive pulmonary tuberculosis
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2023 (Engelska)Ingår i: Trials, E-ISSN 1745-6215, Vol. 24, nr 1, artikel-id 382Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: Linezolid is an effective, but toxic anti-tuberculosis drug that is currently recommended for the treatment of drug-resistant tuberculosis. Improved oxazolidinones should have a better safety profile, while preserving efficacy. Delpazolid is a novel oxazolidinone developed by LegoChem Biosciences Inc. that has been evaluated up to phase 2a clinical trials. Since oxazolidinone toxicity can occur late in treatment, LegoChem Biosciences Inc. and the PanACEA Consortium designed DECODE to be an innovative dose-ranging study with long-term follow-up for determining the exposure-response and exposure-toxicity relationship of delpazolid to support dose selection for later studies. Delpazolid is administered in combination with bedaquiline, delamanid and moxifloxacin.

Methods: Seventy-five participants with drug-sensitive, pulmonary tuberculosis will receive bedaquiline, delamanid and moxifloxacin, and will be randomized to delpazolid dosages of 0 mg, 400 mg, 800 mg, 1200 mg once daily, or 800 mg twice daily, for 16 weeks. The primary efficacy endpoint will be the rate of decline of bacterial load on treatment, measured by MGIT liquid culture time to detection from weekly sputum cultures. The primary safety endpoint will be the proportion of oxazolidinone class toxicities; neuropathy, myelosuppression, or tyramine pressor response. Participants who convert to negative liquid media culture by week 8 will stop treatment after the end of their 16-week course and will be observed for relapse until week 52. Participants who do not convert to negative culture will receive continuation phase treatment with rifampicin and isoniazid to complete a six-month treatment course.

Discussion: DECODE is an innovative dose-finding trial, designed to support exposure-response modelling for safe and effective dose selection. The trial design allows assessment of occurrence of late toxicities as observed with linezolid, which is necessary in clinical evaluation of novel oxazolidinones. The primary efficacy endpoint is the change in bacterial load, an endpoint conventionally used in shorter dose-finding trials. Long-term follow-up after shortened treatment is possible through a safety rule excluding slow-and non-responders from potentially poorly performing dosages.

Ort, förlag, år, upplaga, sidor
BMC, 2023
Nyckelord
Uncomplicated pulmonary tuberculosis, Treatment, Delpazolid, Randomized controlled trial, Phase IIb, Oxazolidinone
Nationell ämneskategori
Farmaceutiska vetenskaper Farmakologi och toxikologi Infektionsmedicin
Identifikatorer
urn:nbn:se:uu:diva-507004 (URN)10.1186/s13063-023-07354-5 (DOI)001003653200003 ()37280643 (PubMedID)
Tillgänglig från: 2023-07-03 Skapad: 2023-07-03 Senast uppdaterad: 2024-01-17Bibliografiskt granskad
Garcia-Prats, A. J., Hoddinott, G., Howell, P., Hughes, J., Jean-Philippe, P., Kim, S., . . . Hesseling, A. C. (2023). Children deserve simple, short, safe, and effective treatment for rifampicin-resistant tuberculosis. The Lancet - Infectious diseases, 23(7), 778-780
Öppna denna publikation i ny flik eller fönster >>Children deserve simple, short, safe, and effective treatment for rifampicin-resistant tuberculosis
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2023 (Engelska)Ingår i: The Lancet - Infectious diseases, ISSN 1473-3099, E-ISSN 1474-4457, Vol. 23, nr 7, s. 778-780Artikel i tidskrift, Editorial material (Övrigt vetenskapligt) Published
Ort, förlag, år, upplaga, sidor
Elsevier, 2023
Nationell ämneskategori
Infektionsmedicin Pediatrik
Identifikatorer
urn:nbn:se:uu:diva-508978 (URN)10.1016/S1473-3099(23)00349-3 (DOI)001032667200001 ()37245523 (PubMedID)
Tillgänglig från: 2023-08-14 Skapad: 2023-08-14 Senast uppdaterad: 2024-01-17Bibliografiskt granskad
Singh, K. P., Carvalho, A. C., Centis, R., D'Ambrosio, L., Migliori, G. B., Mpagama, S. G., . . . Denholm, J. T. (2023). Clinical standards for the management of adverse effects during treatment for TB. The International Journal of Tuberculosis and Lung Disease, 27(7), 506-519
Öppna denna publikation i ny flik eller fönster >>Clinical standards for the management of adverse effects during treatment for TB
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2023 (Engelska)Ingår i: The International Journal of Tuberculosis and Lung Disease, ISSN 1027-3719, E-ISSN 1815-7920, Vol. 27, nr 7, s. 506-519Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

BACKGROUND: Adverse effects (AE) to TB treatment cause morbidity, mortality and treatment interruption. The aim of these clinical standards is to encourage best practise for the diagnosis and management of AE.

METHODS: 65/81 invited experts participated in a Delphi process using a 5-point Likert scale to score draft standards.

RESULTS: We identified eight clinical standards. Each person commencing treatment for TB should: Standard 1, be counselled regarding AE before and during treatment; Standard 2, be evaluated for factors that might increase AE risk with regular review to actively identify and manage these; Standard 3, when AE occur, carefully assessed and possible allergic or hypersensitiv-ity reactions considered; Standard 4, receive appropriate care to minimise morbidity and mortality associated with AE; Standard 5, be restarted on TB drugs after a serious AE according to a standardised protocol that includes active drug safety monitoring. In addition: Standard 6, healthcare workers should be trained on AE including how to counsel people undertaking TB treatment, as well as active AE monitoring and management; Standard 7, there should be active AE monitoring and reporting for all new TB drugs and regimens; and Standard 8, knowledge gaps identified from active AE monitoring should be systematically addressed through clinical research.

CONCLUSION: These standards provide a person -centred, consensus-based approach to minimise the impact of AE TB treatment.

Ort, förlag, år, upplaga, sidor
International Union Against Tuberculosis and Lung Disease, 2023
Nyckelord
tuberculosis, adverse effects, management, toxicity, drugs, safety
Nationell ämneskategori
Samhällsfarmaci och klinisk farmaci
Identifikatorer
urn:nbn:se:uu:diva-509152 (URN)10.5588/ijtld.23.0078 (DOI)001029744100004 ()37353868 (PubMedID)
Tillgänglig från: 2023-08-16 Skapad: 2023-08-16 Senast uppdaterad: 2023-08-16Bibliografiskt granskad
Ayoun Alsoud, R., Svensson, R. J., Svensson, E., Gillespie, S. H. H., Boeree, M. J. J., Diacon, A. H. H., . . . Simonsson, U. S. H. (2023). Combined quantitative tuberculosis biomarker model for time-to-positivity and colony forming unit to support tuberculosis drug development. Frontiers in Pharmacology, 14, Article ID 1067295.
Öppna denna publikation i ny flik eller fönster >>Combined quantitative tuberculosis biomarker model for time-to-positivity and colony forming unit to support tuberculosis drug development
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2023 (Engelska)Ingår i: Frontiers in Pharmacology, E-ISSN 1663-9812, Vol. 14, artikel-id 1067295Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Biomarkers are quantifiable characteristics of biological processes. In Mycobacterium tuberculosis, common biomarkers used in clinical drug development are colony forming unit (CFU) and time-to-positivity (TTP) from sputum samples. This analysis aimed to develop a combined quantitative tuberculosis biomarker model for CFU and TTP biomarkers for assessing drug efficacy in early bactericidal activity studies. Daily CFU and TTP observations in 83 previously patients with uncomplicated pulmonary tuberculosis after 7 days of different rifampicin monotherapy treatments (10-40 mg/kg) from the HIGHRIF1 study were included in this analysis. The combined quantitative tuberculosis biomarker model employed the Multistate Tuberculosis Pharmacometric model linked to a rifampicin pharmacokinetic model in order to determine drug exposure-response relationships on three bacterial sub-states using both the CFU and TTP data simultaneously. CFU was predicted from the MTP model and TTP was predicted through a time-to-event approach from the TTP model, which was linked to the MTP model through the transfer of all bacterial sub-states in the MTP model to a one bacterial TTP model. The non-linear CFU-TTP relationship over time was well predicted by the final model. The combined quantitative tuberculosis biomarker model provides an efficient approach for assessing drug efficacy informed by both CFU and TTP data in early bactericidal activity studies and to describe the relationship between CFU and TTP over time.

Ort, förlag, år, upplaga, sidor
Frontiers Media S.A., 2023
Nyckelord
rifampicin, TTP, CFU, tuberculosis, biomarker
Nationell ämneskategori
Farmakologi och toxikologi Farmaceutiska vetenskaper
Identifikatorer
urn:nbn:se:uu:diva-500588 (URN)10.3389/fphar.2023.1067295 (DOI)000959380900001 ()36998606 (PubMedID)
Tillgänglig från: 2023-04-21 Skapad: 2023-04-21 Senast uppdaterad: 2024-03-11Bibliografiskt granskad
Stemkens, R., de Jager, V., Dawson, R., Diacon, A. H., Narunsky, K., Padayachee, S. D., . . . Aarnoutse, R. E. (2023). Drug interaction potential of high-dose rifampicin in patients with pulmonary tuberculosis. Antimicrobial Agents and Chemotherapy, 67(10), Article ID e0068323.
Öppna denna publikation i ny flik eller fönster >>Drug interaction potential of high-dose rifampicin in patients with pulmonary tuberculosis
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2023 (Engelska)Ingår i: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 67, nr 10, artikel-id e0068323Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Accumulating evidence supports the use of higher doses of rifampicin for tuberculosis (TB) treatment. Rifampicin is a potent inducer of metabolic enzymes and drug transporters, resulting in clinically relevant drug interactions. To assess the drug interaction potential of higher doses of rifampicin, we compared the effect of high-dose rifampicin (40 mg/kg daily, RIF40) and standard-dose rifampicin (10 mg/kg daily, RIF10) on the activities of major cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp). In this open-label, single-arm, two-period, fixed-order phenotyping cocktail study, adult participants with pulmonary TB received RIF10 (days 1–15), followed by RIF40 (days 16–30). A single dose of selective substrates (probe drugs) was administered orally on days 15 and 30: caffeine (CYP1A2), tolbutamide (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), midazolam (CYP3A), and digoxin (P-gp). Intensive pharmacokinetic blood sampling was performed over 24 hours after probe drug intake. In all, 25 participants completed the study. Geometric mean ratios (90% confidence interval) of the total exposure (area under the concentration versus time curve, RIF40 versus RIF10) for each of the probe drugs were as follows: caffeine, 105% (96%–115%); tolbutamide, 80% (74%–86%); omeprazole, 55% (47%–65%); dextromethorphan, 77% (68%–86%); midazolam, 62% (49%–78%), and 117% (105%–130%) for digoxin. In summary, high-dose rifampicin resulted in no additional effect on CYP1A2, mild additional induction of CYP2C9, CYP2C19, CYP2D6, and CYP3A, and marginal inhibition of P-gp. Existing recommendations on managing drug interactions with rifampicin can remain unchanged for the majority of co-administered drugs when using high-dose rifampicin. Clinical Trials registration number NCT04525235.

Ort, förlag, år, upplaga, sidor
American Society for Microbiology, 2023
Nyckelord
tuberculosis, high-dose rifampicin, drug interactions, metabolic phenotyping
Nationell ämneskategori
Farmakologi och toxikologi Farmaceutiska vetenskaper Lungmedicin och allergi
Identifikatorer
urn:nbn:se:uu:diva-522989 (URN)10.1128/aac.00683-23 (DOI)001145398400001 ()37768317 (PubMedID)
Forskningsfinansiär
Europeiska kommissionen, TRIA2015-1102-PanACEA
Tillgänglig från: 2024-02-13 Skapad: 2024-02-13 Senast uppdaterad: 2024-02-13Bibliografiskt granskad
Koele, S. E., Phillips, P. P. J., Upton, C. M., van Ingen, J., Simonsson, U. S. H., Diacon, A. H., . . . Svensson, E. M. (2023). Early bactericidal activity studies for pulmonary tuberculosis: A systematic review of methodological aspects. International Journal of Antimicrobial Agents, 61(5), Article ID 106775.
Öppna denna publikation i ny flik eller fönster >>Early bactericidal activity studies for pulmonary tuberculosis: A systematic review of methodological aspects
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2023 (Engelska)Ingår i: International Journal of Antimicrobial Agents, ISSN 0924-8579, E-ISSN 1872-7913, Vol. 61, nr 5, artikel-id 106775Artikel, forskningsöversikt (Refereegranskat) Published
Abstract [en]

A milestone in the development of novel antituberculosis drugs is the demonstration of early bactericidal activity (EBA) in a phase IIa clinical trial. The significant variability in measurements of bacterial load complicates data analysis in these trials.

A systematic review and evaluation of methods for determination of EBA in pulmonary tuberculosis studies was undertaken. Bacterial load quantification biomarkers, reporting intervals, calculation methods, statistical testing, and handling of negative culture results were extracted. In total, 79 studies were identi-fied in which EBA was determined. Colony-forming units on solid culture media and/or time-to-positivity in liquid media were the biomarkers used most often, reported in 72 (91%) and 34 (43%) studies, respec-tively. Twenty-two different reporting intervals were presented, and 12 different calculation methods for EBA were identified. Statistical testing for a significant EBA compared with no change was performed in 54 (68%) studies, and between-group testing was performed in 32 (41%) studies. Negative culture result handling was discussed in 34 (43%) studies.

Notable variation was found in the analysis methods and reporting of EBA studies. A standardized and clearly reported analysis method, accounting for different levels of variability in the data, could aid the generalization of study results and facilitate comparison between drugs/regimens.

Ort, förlag, år, upplaga, sidor
Elsevier, 2023
Nyckelord
Tuberculosis, Early bactericidal activity, Analysis methods, Reporting
Nationell ämneskategori
Farmaceutiska vetenskaper Mikrobiologi inom det medicinska området Infektionsmedicin
Identifikatorer
urn:nbn:se:uu:diva-504018 (URN)10.1016/j.ijantimicag.2023.106775 (DOI)000981961700001 ()36893811 (PubMedID)
Tillgänglig från: 2023-06-16 Skapad: 2023-06-16 Senast uppdaterad: 2023-06-16Bibliografiskt granskad
Prins, H. A., Zino, L., Svensson, E. M., Verbon, A., de Bree, G. J., Prins, J. M., . . . Team, N. S. (2023). Exposure and virologic outcomes of dolutegravir combined with ritonavir boosted darunavir in treatment-naive individuals enrolled in the Netherlands Cohort Study on Acute HIV infection (NOVA). International Journal of Antimicrobial Agents, 61(1), Article ID 106697.
Öppna denna publikation i ny flik eller fönster >>Exposure and virologic outcomes of dolutegravir combined with ritonavir boosted darunavir in treatment-naive individuals enrolled in the Netherlands Cohort Study on Acute HIV infection (NOVA)
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2023 (Engelska)Ingår i: International Journal of Antimicrobial Agents, ISSN 0924-8579, E-ISSN 1872-7913, Vol. 61, nr 1, artikel-id 106697Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

To the authors' knowledge, there is currently no literature or guidance recommendation regard-ing whether the dose of dolutegravir (DTG) should be increased when co-administered with darunavir/ritonavir (DRV/r) in patients with acute human immunodeficiency virus infection (AHI). This study assessed the pharmacokinetics (PK) of twice-daily (BID) DTG and once-daily (QD) DRV/r, and com-pared this with DTG QD without DRV/r in patients with AHI. Forty-six participants initiated antiretro-viral therapy within < 24 h of enrolment: DTG 50 mg BID, DRV/r 80 0/10 0 mg QD, and two nucleoside reverse transcriptase inhibitors (NRTIs) for 4 weeks (Phase I); and DTG 50 mg QD with two NRTIs there-after (Phase II: reference). Total DTG trough concentration (Ctrough) and area under the concentration-time profile of 0-24 h (AUC0-24h) were predicted using a population PK model. DTG glucuronidation metabolic ratio (MR) and DTG free fraction were determined and compared per treatment phase using geometric mean ratio (GMR) and 90% confidence interval (CI). Participants had a predicted geometric mean steady-state DTG Ctrough of 2.83 [coefficient of variation (CV%) 30.3%] mg/L (Phase I) and 1.28 (CV% 52.4%) mg/L (Phase II), with GMR of 2.20 (90% CI 1.90-2.55). Total exposure during DTG BID increased but did not double [AUC0-24h GMR 1.65 (90% CI 1.50-1.81) h.mg/L]. DTG glucuronidation MR increased by approxi-mately 29% during Phase I. DTG Ctrough was above in-vivo EC90 (0.32 mg/L) during both phases, except in one participant during Phase I. At Week 8, 84% of participants had viral loads <= 40 copies/mL. The drug-drug interaction between DTG (BID) and DRV/r (QD) was due to induced glucuronidation, and is not clinically relevant in patients with AHI.(c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

Ort, förlag, år, upplaga, sidor
Elsevier, 2023
Nyckelord
Darunavir, ritonavir, Acute HIV infection, Dolutegravir, Population PK
Nationell ämneskategori
Infektionsmedicin
Identifikatorer
urn:nbn:se:uu:diva-495898 (URN)10.1016/j.ijantimicag.2022.106697 (DOI)000910030500001 ()36470510 (PubMedID)
Tillgänglig från: 2023-02-07 Skapad: 2023-02-07 Senast uppdaterad: 2023-02-07Bibliografiskt granskad
Gafar, F., Wasmann, R. E., McIlleron, H. M., Aarnoutse, R. E., Schaaf, H. S., Marais, B. J., . . . Alffenaar, J.-W. C. (2023). Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis. European Respiratory Journal, 61(3), Article ID 2201596.
Öppna denna publikation i ny flik eller fönster >>Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis
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2023 (Engelska)Ingår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 61, nr 3, artikel-id 2201596Artikel, forskningsöversikt (Refereegranskat) Published
Abstract [en]

Background Suboptimal exposure to antituberculosis (anti-TB) drugs has been associated with unfavourable treatment outcomes. We aimed to investigate estimates and determinants of first-line anti-TB drug pharmacokinetics in children and adolescents at a global level.

Methods We systematically searched MEDLINE, Embase and Web of Science (1990–2021) for pharmacokinetic studies of first-line anti-TB drugs in children and adolescents. Individual patient data were obtained from authors of eligible studies. Summary estimates of total/extrapolated area under the plasma concentration–time curve from 0 to 24 h post-dose (AUC0–24) and peak plasma concentration (Cmax) were assessed with random-effects models, normalised with current World Health Organization-recommended paediatric doses. Determinants of AUC0–24 and Cmax were assessed with linear mixed-effects models.

Results Of 55 eligible studies, individual patient data were available for 39 (71%), including 1628 participants from 12 countries. Geometric means of steady-state AUC0–24 were summarised for isoniazid (18.7 (95% CI 15.5–22.6) h·mg·L−1), rifampicin (34.4 (95% CI 29.4–40.3) h·mg·L−1), pyrazinamide (375.0 (95% CI 339.9–413.7) h·mg·L−1) and ethambutol (8.0 (95% CI 6.4–10.0) h·mg·L−1). Our multivariate models indicated that younger age (especially <2 years) and HIV-positive status were associated with lower AUC0–24 for all first-line anti-TB drugs, while severe malnutrition was associated with lower AUC0–24 for isoniazid and pyrazinamide. N-acetyltransferase 2 rapid acetylators had lower isoniazid AUC0–24 and slow acetylators had higher isoniazid AUC0–24 than intermediate acetylators. Determinants of Cmax were generally similar to those for AUC0–24.

Conclusions This study provides the most comprehensive estimates of plasma exposures to first-line anti-TB drugs in children and adolescents. Key determinants of drug exposures were identified. These may be relevant for population-specific dose adjustment or individualised therapeutic drug monitoring.

Ort, förlag, år, upplaga, sidor
European Respiratory Society, 2023
Nationell ämneskategori
Farmaceutiska vetenskaper
Identifikatorer
urn:nbn:se:uu:diva-510813 (URN)10.1183/13993003.01596-2022 (DOI)001042678600001 ()36328357 (PubMedID)
Forskningsfinansiär
Wellcome trust
Tillgänglig från: 2023-09-04 Skapad: 2023-09-04 Senast uppdaterad: 2024-01-26Bibliografiskt granskad
Susanto, B. O., Svensson, E. M., te Brake, L., Aarnoutse, R. E., Boeree, M. J. & Simonsson, U. S. H. (2023). Model-based analysis of bactericidal activity and a new dosing strategy for optimised-dose rifampicin. International Journal of Antimicrobial Agents, 61(6), Article ID 106813.
Öppna denna publikation i ny flik eller fönster >>Model-based analysis of bactericidal activity and a new dosing strategy for optimised-dose rifampicin
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2023 (Engelska)Ingår i: International Journal of Antimicrobial Agents, ISSN 0924-8579, E-ISSN 1872-7913, Vol. 61, nr 6, artikel-id 106813Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background

Higher doses of rifampicin for tuberculosis have been shown to improve early bactericidal activity (EBA) and at the same time increase the intolerability due to high exposure at the beginning of treatment. To support dose optimisation of rifampicin, this study investigated new and innovative staggered dosing of rifampicin using clinical trial simulations to minimise tolerability problems and still achieve good efficacy.

Methods

Rifampicin population pharmacokinetics and time-to-positivity models were applied to data from patients receiving 14 days of daily 10–50 mg/kg rifampicin to characterise the exposure-response relationship. Furthermore, clinical trial simulations of rifampicin exposure were performed following four different staggered dosing scenarios. The simulated exposure after 35 mg/kg was used as a relative comparison for efficacy. Tolerability was derived from a previous model-based analysis relating exposure at day 7 and the probability of having adverse events.

Results

The linear relationship between rifampicin exposure and bacterial killing rate in sputum indicated that the maximum rifampicin EBA was not reached at doses up to 50 mg/kg. Clinical trial simulations of a staggered dosing strategy starting the treatment at a lower dose (20 mg/kg) for 7 days followed by a higher dose (40 mg/kg) predicted a lower initial exposure with lower probability of tolerability problems and better EBA compared with a regimen of 35 mg/kg daily.

Conclusions

Staggered dosing of 20 mg/kg for 7 days followed by 40 mg/kg is predicted to reduce tolerability while maintaining exposure levels associated with better efficacy.

Ort, förlag, år, upplaga, sidor
Elsevier, 2023
Nyckelord
Staggered dosing, Rifampicin, Tuberculosis, Model-based analysis, Clinical trial simulation
Nationell ämneskategori
Farmakologi och toxikologi Farmaceutiska vetenskaper Infektionsmedicin
Identifikatorer
urn:nbn:se:uu:diva-504963 (URN)10.1016/j.ijantimicag.2023.106813 (DOI)000997767700001 ()37037318 (PubMedID)
Forskningsfinansiär
Vetenskapsrådet, 2018-05973
Tillgänglig från: 2023-06-19 Skapad: 2023-06-19 Senast uppdaterad: 2023-06-19Bibliografiskt granskad
Diaz, J. M. A., Abulfathi, A. A., te Brake, L. H. M., van Ingen, J., Kuipers, S., Magis-Escurra, C., . . . Boeree, M. J. (2023). New and Repurposed Drugs for the Treatment of Active Tuberculosis: An Update for Clinicians. Respiration, 102(2), 83-100
Öppna denna publikation i ny flik eller fönster >>New and Repurposed Drugs for the Treatment of Active Tuberculosis: An Update for Clinicians
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2023 (Engelska)Ingår i: Respiration, ISSN 0025-7931, E-ISSN 1423-0356, Vol. 102, nr 2, s. 83-100Artikel, forskningsöversikt (Refereegranskat) Published
Abstract [en]

Although tuberculosis (TB) is preventable and curable, the lengthy treatment (generally 6 months), poor patient adherence, high inter-individual variability in pharmacokinetics (PK), emergence of drug resistance, presence of comorbidities, and adverse drug reactions complicate TB therapy and drive the need for new drugs and/or regimens. Hence, new compounds are being developed, available drugs are repurposed, and the dosing of existing drugs is optimized, resulting in the largest drug development portfolio in TB history. This review highlights a selection of clinically available drug candidates that could be part of future TB regimens, including bedaquiline, delamanid, pretomanid, linezolid, clofazimine, optimized (high dose) rifampicin, rifapentine, and para-aminosalicylic acid. The review covers drug development history, preclinical data, PK, and current clinical development.

Ort, förlag, år, upplaga, sidor
S. Karger, 2023
Nyckelord
Drugs, Treatment, Tuberculosis
Nationell ämneskategori
Farmaceutiska vetenskaper Farmakologi och toxikologi
Identifikatorer
urn:nbn:se:uu:diva-502447 (URN)10.1159/000528274 (DOI)000897216300001 ()36516792 (PubMedID)
Tillgänglig från: 2023-05-25 Skapad: 2023-05-25 Senast uppdaterad: 2023-05-25Bibliografiskt granskad
Organisationer
Identifikatorer
ORCID-id: ORCID iD iconorcid.org/0000-0002-0093-6445

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