Penetration levels and concentration of bedaquiline and clofazimine into the brain parenchyma compared with those in blood plasma: a systematic review and individual case report analysis

The absence of a clear summary of the pharmacokinetic-pharmacodynamic (PK/PD) properties of bedaquiline (Bdq) and clofazimine (Cfz) has limited their use in treating
tuberculosis meningitis. This study is the first to summarize the pharmacokinetics and pharmacodynamics of Bdq and Cfz in the cerebrospinal fluid (CSF) and serum. Despite the few reports and studies conducted, we need clear evidence of the PK/PD properties to believe why these drugs must be considered. The included studies report the PK/PD properties of Bedaquiline and or Clofazimine in the blood plasma and or in the brain parenchyma. We exclude non-English articles, papers from non-English speaking countries, and publications before 2000. In this systematic review, we searched articles from PubMed, Scopus, Web of
Science, and Google Scholar for studies published from 2000 to Sept 20th, 2023 that assessed treatments and experiments including using bedaquiline “AND” “OR” clofazimine. We also
reported studies that included animals in the experimental setting. The risk of Bias in the extracted data was independently assessed by the authors via the EQUATOR (Enhancing the Quality and Transparency of Health Research) study protocol and visualized with Robvis tools.
We found nine studies that were suitable for our inclusion criteria. Among nine studies we reviewed, Bedaquiline has a better penetrating ability into the brain parenchyma and central nervous system (CNS) and yields a higher concentration than clofazimine. This study has
limitations, including the use of a combination of both drugs where few reports are available. Moreover, further studies are needed to evaluate the efficacy of Bdq and Cfz in the treatment of TBM. All studies were carried out systematically following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and were registered in the PROSPERO database CRD42023466389.