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Clin Pharmacol Drug Dev 2019 05 30;8(4):436-442. Epub 2018 Nov 30.

Department of Pediatrics, University of Toledo College of Medicine, Toledo, OH, USA.

There is an urgent need to identify safe and effective combination treatments for multidrug-resistant (MDR) Mycobacterium tuberculosis infection (TB). Bedaquiline, a new diarylquinoline, is approved for the treatment of MDR pulmonary TB in combination with other drugs, which could include rifabutin, which is also used to treat drug-resistant TB. Both rifabutin and bedaquiline are metabolized via cytochrome P450 3A4, and rifabutin is an inducer of this enzyme. Read More

PLoS One 2018 2;13(5):e0196756. Epub 2018 May 2.

School of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, Ohio, United States of America.

Background: Bedaquiline, an antimycobacterial agent approved for drug-resistant tuberculosis, is metabolized by CYP3A4, an hepatic enzyme strongly induced by rifampin, an essential part of drug-sensitive tuberculosis treatment. We examined the pharmacokinetic interactions of bedaquiline plus either rifampin or rifabutin in 33 healthy volunteers. This sub-study of that trial examined the mycobactericidal activity of these drugs against intracellular Mycobacterium tuberculosis using ex vivo whole blood culture. Read More

Expert Rev Clin Pharmacol 2016 Aug 27;9(8):1025-37. Epub 2016 Jun 27.

f University of Groningen, University Medical Center Groningen, Clinical Pharmacy and Pharmacology , Groningen , The Netherlands.

Introduction: Few innovative anti-microbial products have been brought to market in recent years to combat the global multidrug resistant-tuberculosis (MDR-TB) epidemic. Bedaquiline, a novel oral diarylquinoline, was approved by the US FDA as a part of combination therapy in adults with pulmonary MDR-TB based on phase II trials.

Area Covered: Pubmed searches were conducted using search terms bedaquiline, diarylquinoline, R207910, and TMC207 was performed. Read More

J Antimicrob Chemother 2016 Apr 7;71(4):1037-40. Epub 2016 Jan 7.

Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa

Objectives: Bedaquiline is a new anti-TB drug, which is metabolized by cytochrome P450 (CYP) 3A4. Concomitant ART is important for all HIV-infected patients treated for TB, but several antiretrovirals inhibit or induce CYP3A4. Single-dose drug-drug interaction studies found no significant interactions with nevirapine or lopinavir/ritonavir, but these findings could be misleading, especially because of bedaquiline's long terminal t1/2. Read More

J Antimicrob Chemother 2015 Apr 21;70(4):1106-14. Epub 2014 Dec 21.

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Objectives: Bedaquiline is the first drug of a new class approved for the treatment of TB in decades. Bedaquiline is metabolized by cytochrome P450 (CYP) 3A4 to a less-active M2 metabolite. Its terminal half-life is extremely long (5-6 months), complicating evaluations of drug-drug interactions. Read More