期刊
CLINICAL PHARMACOLOGY IN DRUG DEVELOPMENT
卷 10, 期 6, 页码 634-646出版社
WILEY
DOI: 10.1002/cpdd.898
关键词
pretomanid; PA‐ 824; moxifloxacin; thorough QT study; tuberculosis
资金
- United StatesNational Institute of Allergy and Infectious Diseases [HHSN272200800024C]
- TB Alliance
- Australia's Department of Foreign Affairs and Trade
- Bill& Melinda Gates Foundation
- Germany's FederalMinistry of Education and Research through KfW
- Irish Aid
- Netherlands Ministry of Foreign Affairs
- United Kingdom Department for International Development
Tuberculosis remains a serious threat to global public health, requiring new treatment options. Research showed that Pretomanid demonstrated good cardiac safety in healthy volunteers, with no adverse effects when used in combination with other drugs.
Tuberculosis (TB) continues to be a serious threat to public health throughout the world. Newer treatments are needed that could offer simplified regimens with activity against both drug-sensitive and drug-resistant bacilli, while optimizing safety. Pretomanid (PA-824), a nitroimidazooxazine compound, is a new drug for the treatment of pulmonary TB that was recently approved in the United States and Europe in the context of a regimen combined with bedaquiline and linezolid. This phase 1 double-blind, randomized, placebo-controlled crossover study specifically examined the effect of single-dose administration of pretomanid 400 or 1000 mg and pretomanid 400 mg plus moxifloxacin 400 mg on the QTc interval in 74 healthy subjects. Subjects were fasting at the time of drug administration. Pretomanid concentrations following single 400- or 1000-mg doses were not associated with any QT interval prolongation of clinical concern. Moxifloxacin did not alter the pharmacokinetics of pretomanid, and the effect of pretomanid 400 mg plus moxifloxacin 400 mg on the individually corrected QT interval was consistent with the effect of moxifloxacin alone. Both drugs were generally well tolerated. Although supratherapeutic exposure of pretomanid relative to the now-recommended dosing with food was not achieved, these findings contribute to the favorable assessment of cardiac safety for pretomanid.
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