liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Population Pharmacokinetics and Dose Evaluation of Cycloserine among Patients with Multidrug-Resistant Tuberculosis under Standardized Treatment Regimens
Fudan Univ, Peoples R China; Fudan Univ, Peoples R China.
Jiangsu Prov Ctr Dis Control & Prevent, Peoples R China.
Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.ORCID iD: 0000-0001-6069-3564
Show others and affiliations
2023 (English)In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 67, no 5Article in journal (Refereed) Published
Abstract [en]

Although cycloserine is a recommended drug for the treatment of multidrug-resistant tuberculosis (MDR-TB) according to World Health Organization (WHO), few studies have reported on pharmacokinetics (PK) and/or pharmacodynamics (PD) data of cycloserine in patients with standardized MDR-TB treatment. This study aimed to estimate the population PK parameters for cycloserine and to identify clinically relevant PK/PD thresholds, as well as to evaluate the current recommended dosage. Although cycloserine is a recommended drug for the treatment of multidrug-resistant tuberculosis (MDR-TB) according to World Health Organization (WHO), few studies have reported on pharmacokinetics (PK) and/or pharmacodynamics (PD) data of cycloserine in patients with standardized MDR-TB treatment. This study aimed to estimate the population PK parameters for cycloserine and to identify clinically relevant PK/PD thresholds, as well as to evaluate the current recommended dosage. Data from a large cohort with full PK curves was used to develop a population PK model. This model was used to estimate drug exposure in patients with MDR-TB from a multicentre prospective study in China. The classification and regression tree was used to identify the clinically relevant PK/PD thresholds. Probability of target attainment was analyzed to evaluate the currently recommended dosing strategy. Cycloserine was best described by a two-compartment disposition model. A percentage of time concentration above MICs (T->MIC) of 30% and a ratio of area under drug concentration-time curve (AUC(0-24h)) over MIC of 36 were the valid predictors for 6-month sputum culture conversion and final treatment outcome. Simulations showed that with WHO-recommended doses (500 mg and 750 mg for patients weighing <45 kg and >= 45 kg), the probability of target attainment exceeded 90% at MIC <= 16 mg/L in MGIT for both T->MIC of 30% and AUC(0-24h)/MIC of 36. New clinically relevant PK/PD thresholds for cycloserine were identified in patients with standardized MDR-TB treatment. WHO-recommended doses were considered adequate for the MGIT MIC distribution in our cohort of Chinese patients with MDR-TB.

Place, publisher, year, edition, pages
AMER SOC MICROBIOLOGY , 2023. Vol. 67, no 5
Keywords [en]
cycloserine; multidrug-resistant tuberculosis; minimum inhibitory concentration; population pharmacokinetics; drug concentration thresholds; dosing evaluation
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:liu:diva-194457DOI: 10.1128/aac.01700-22ISI: 000975278200001PubMedID: 37097151OAI: oai:DiVA.org:liu-194457DiVA, id: diva2:1764732
Note

Funding Agencies|National Natural Science Foundation of China [81874273]; Swedish Research Council; Swedish Heart and Lung Foundation; County of Stockholm; Research Council of south-eastern Sweden

Available from: 2023-06-09 Created: 2023-06-09 Last updated: 2024-02-09

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Paues, JakobNiward, KatarinaSchön, Thomas
By organisation
Division of Inflammation and InfectionFaculty of Medicine and Health SciencesDepartment of Infectious Diseases
In the same journal
Antimicrobial Agents and Chemotherapy
Pharmaceutical Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 46 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf