Relationship between oral administration of garenoxacin and QT interval

Abstract

The effect of garenoxacin mesilate hydrate (GRNX), a novel quinolone antimicrobial, on QT interval was investigated. Electrocardiogram data from 66 healthy volunteers was analyzed in the clinical pharmacology study, and 504 patients who received 400mg/dose/day in phase III clinical trials on infected patients.
At around Tmax (two hours after administration) of the single dose study, in the subject group who received 600mg administration, the mean QTc was 365.8 ± 26.9msec, and the mean ΔQTc was-1.8±25.4 msec, and did not have the tendency to prolong QTc.
The mean d QTc of phase III clinical studies were-10.5 ± 27.0msec at three days after administration, and-9.0 ± 27.8msec at nine days after administration, and there was no tendency of prolongation.
In an analysis by category, there were three of 504 patients in phase III clinical trials who had QTc exceeding 450msec (470msec: females) and ΔQTc exceeded 60 msec, but these QTc and d QTc were due to a clinical background.
In an investigation on the relationship between ΔQTc and the plasma concentration of the drug, no correlation was observed. No significant changes in the electrocardiogram wave pattern by this drug or adverse events related to QTc prolongation were observed. No correlation was observed between QTc or ΔQTc, and age or weight distribution of patients.
From these observations, we conclude that GRNX has no appreciable effect on QTc intervals.