uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • 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
Pharmacokinetic interaction between bedaquiline and clofazimine in patients with drug-resistant tuberculosis
Univ Cape Town, Dept Med, Div Clin Pharmacol, Cape Town, South Africa.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Univ Cape Town, Dept Med, Div Clin Pharmacol, Cape Town, South Africa.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Dept Pharm, Nijmegen, Netherlands.
2018 (English)In: The International Journal of Tuberculosis and Lung Disease, ISSN 1027-3719, E-ISSN 1815-7920, Vol. 22, no 1, p. 26-29Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Bedaquiline (BDQ) and clofazimine (CFZ) are both recommended for treating drug-resistant tuberculosis (DR-TB). As CFZ is an inhibitor of the cytochrome P450 isoenzyme 3A4 (CYP3A4) in vitro, and BDQ a substrate of CYP3A4, there is a potential for pharmacokinetic (PK) drug-drug interaction that may result in increased BDQ exposure when co-administered with CFZ, which could increase the toxicity of BDQ. METHODS : We assessed the effect of co-administered CFZ on BDQ bioavailability, or on clearance of BDQ and its N-monodesmethyl metabolite (M2), in patients with DR-TB using a population PK model developed from data of patients with DR-TB. This was a secondary analysis of a study designed to explore drug-drug interactions between BDQ and antiretrovirals. RESULTS : Of 46 participants, 30 were on concomitant CFZ when intensive PK sampling of BDQ was done. CFZ did not have a statistically significant effect on BDQ bioavailability (-9.1%, 90% CI - 22.8 to +7.1; P = 0.19) or on BDQ and M2 clearance (+12.2%, 90% CI -13.7 to +38; P = 0.32). CONCLUSION: We did not find a statistically significant PK drug-drug interaction between BDQ and CFZ, but cannot exclude a potentially clinically relevant interaction due to the wide confidence intervals of the estimated interaction effects.

Place, publisher, year, edition, pages
INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) , 2018. Vol. 22, no 1, p. 26-29
Keywords [en]
population pharmacokinetics, drug-drug interaction, BDQ, CFZ, TB
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-352999DOI: 10.5588/ijtld.17.0615ISI: 000429780700008PubMedID: 29145924OAI: oai:DiVA.org:uu-352999DiVA, id: diva2:1232980
Available from: 2018-07-13 Created: 2018-07-13 Last updated: 2018-07-13Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed
By organisation
Department of Pharmaceutical Biosciences
In the same journal
The International Journal of Tuberculosis and Lung Disease
Pharmacology and Toxicology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 4 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • 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