Bedaquiline: a review of human pharmacokinetics and drug-drug interactions

Bedaquiline has recently been approved for the treatment of pulmonary multidrug-resistant tuberculosis (TB) as part of combination therapy in adults. It is metabolized primarily by the cytochrome P450 isoenzyme 3A4 (CYP3A4) to a less-active N-monodesmethyl metabolite. Phase I and Phase II studies in...

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Vydáno v:Journal of antimicrobial chemotherapy Ročník 69; číslo 9; s. 2310
Hlavní autoři: van Heeswijk, R P G, Dannemann, B, Hoetelmans, R M W
Médium: Journal Article
Jazyk:angličtina
Vydáno: England 01.09.2014
Témata:
Antifungal Agents - pharmacology
Antitubercular Agents - pharmacokinetics
Antitubercular Agents - pharmacology
Antiviral Agents - pharmacology
Clinical Trials, Phase I as Topic
Clinical Trials, Phase II as Topic
Diarylquinolines - pharmacokinetics
Diarylquinolines - pharmacology
Drug Interactions
Humans
Tuberculosis, Multidrug-Resistant - drug therapy
CYP3A
clinical trials
HIV
tuberculosis
ISSN:1460-2091, 1460-2091
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Shrnutí:Bedaquiline has recently been approved for the treatment of pulmonary multidrug-resistant tuberculosis (TB) as part of combination therapy in adults. It is metabolized primarily by the cytochrome P450 isoenzyme 3A4 (CYP3A4) to a less-active N-monodesmethyl metabolite. Phase I and Phase II studies in healthy subjects and patients with drug-susceptible or multidrug-resistant TB have assessed the pharmacokinetics and drug-drug interaction profile of bedaquiline. Potential interactions have been assessed between bedaquiline and first- and second-line anti-TB drugs (rifampicin, rifapentine, isoniazid, pyrazinamide, ethambutol, kanamycin, ofloxacin and cycloserine), commonly used antiretroviral agents (lopinavir/ritonavir, nevirapine and efavirenz) and a potent CYP3A inhibitor (ketoconazole). This review summarizes the pharmacokinetic profile of bedaquiline as well as the results of the drug-drug interaction studies.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ObjectType-Review-3
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ISSN:1460-2091
1460-2091
DOI:10.1093/jac/dku171