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  • Cardiac drug-drug interaction between HCV-NS5B pronucleotide inhibitors and amiodarone is determined by their specific diastereochemistry.

Cardiac drug-drug interaction between HCV-NS5B pronucleotide inhibitors and amiodarone is determined by their specific diastereochemistry.

Scientific reports (2017-03-23)
Armando Lagrutta, Christopher P Regan, Haoyu Zeng, John P Imredy, Kenneth Koeplinger, Pierre Morissette, Liping Liu, Gordon Wollenberg, Christopher Brynczka, José Lebrón, Joseph DeGeorge, Frederick Sannajust
ABSTRACT

Severe bradycardia/bradyarrhythmia following coadministration of the HCV-NS5B prodrug sofosbuvir with amiodarone was recently reported. Our previous preclinical in vivo experiments demonstrated that only certain HCV-NS5B prodrugs elicit bradycardia when combined with amiodarone. In this study, we evaluate the impact of HCV-NS5B prodrug phosphoramidate diastereochemistry (D-/L-alanine, R-/S-phosphoryl) in vitro and in vivo. Co-applied with amiodarone, L-ala,S

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Fibronectin bovine plasma, solution, sterile-filtered, BioReagent, suitable for cell culture