QT Interval Shortening With Isavuconazole: In Vitro and In Vivo Effects on Cardiac Repolarization.
Article Details
- CitationCopy to clipboard
Keirns J, Desai A, Kowalski D, Lademacher C, Mujais S, Parker B, Schneidkraut MJ, Townsend R, Wojtkowski T, Yamazaki T, Yen M, Kowey PR
QT Interval Shortening With Isavuconazole: In Vitro and In Vivo Effects on Cardiac Repolarization.
Clin Pharmacol Ther. 2017 Jun;101(6):782-790. doi: 10.1002/cpt.620. Epub 2017 Feb 13.
- PubMed ID
- 28074556 [ View in PubMed]
- Abstract
The effects of isavuconazole (active moiety of isavuconazonium sulfate) on cardiac ion channels in vitro and cardiac repolarization clinically were assessed in a phase I, randomized, double-blind study in healthy individuals who received isavuconazole (after 2-day loading dose), at therapeutic or supratherapeutic doses daily for 11 days, moxifloxacin (400 mg q.d.), or placebo. A post-hoc analysis of the phase III SECURE trial assessed effects on cardiac safety. L-type Ca(2+) channels were most sensitive to inhibition by isavuconazole. The 50% inhibitory concentrations for ion channels were higher than maximum serum concentrations of nonprotein-bound isavuconazole in vivo. In the phase I study (n = 161), isavuconazole shortened the QT interval in a dose- and plasma concentration-related manner. There were no serious treatment-emergent adverse events; palpitations and tachycardia were observed in placebo and supratherapeutic isavuconazole groups; no cardiac safety signals were detected in the SECURE study (n = 257). Isavuconazole was associated with a shortened cardiac QT interval.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Isavuconazole ATP-sensitive inward rectifier potassium channel 11 Protein Humans NoInhibitorDetails Isavuconazole G protein-activated inward rectifier potassium channel 2 Protein Humans NoInhibitorDetails Isavuconazole G protein-activated inward rectifier potassium channel 3 Protein Humans NoInhibitorDetails Isavuconazole Potassium voltage-gated channel subfamily A member 5 Protein Humans NoInhibitorDetails Isavuconazole Potassium voltage-gated channel subfamily D member 3 Protein Humans NoInhibitorDetails Isavuconazole Potassium voltage-gated channel subfamily H member 2 Protein Humans NoInhibitorDetails Isavuconazole Potassium voltage-gated channel subfamily KQT member 1 Protein Humans NoInhibitorDetails Isavuconazole Sodium channel protein type 5 subunit alpha Protein Humans NoInhibitorDetails Isavuconazole Voltage-dependent L-type calcium channel subunit alpha-1C Protein Humans NoInhibitorDetails