Usefulness of simultaneous and sequential monitoring of ... - J-Stage
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Usefulness of simultaneous and sequential monitoring of ... - J-Stage
in monkeys treated with gatifloxacin under conscious and nonrestricted conditions. Yu Yoshimatsu, tomomichi ishizaka, katsuyoshi Chiba, and kazuhiko mori.
Exp. Anim. 67(2), 281–290, 2018
—Original—
Usefulness of simultaneous and sequential monitoring of glucose level and electrocardiogram in monkeys treated with gatifloxacin under conscious and nonrestricted conditions Yu Yoshimatsu, Tomomichi Ishizaka, Katsuyoshi Chiba, and Kazuhiko Mori Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., 1-16-13 Kita-Kasai, Edogawa-ku, Tokyo 134-8630, Japan
Abstract: Drug-induced cardiac electrophysiological abnormalities accompanied by hypoglycemia or hyperglycemia increase the risk for life-threatening arrhythmia. To assess the drug-induced cardiotoxic potential associated with extraordinary blood glucose (GLU) levels, the effect of gatifloxacin (GFLX) which was frequently associated with GLU abnormality and QT/QTc prolongations in the clinic on blood GLU and electrocardiogram (ECG) parameters was investigated in cynomolgus monkeys (n=4) given GFLX orally in an ascending dose regimen (10, 30, 60 and 100 mg/kg). Simultaneous and sequential GLU and ECG monitoring with a continuous GLU monitoring system and Holter ECG, respectively, were conducted for 24 h under free-moving conditions. Consequently, GFLX at 30 and 60 mg/kg dose-dependently induced a transient decrease in GLU without any ECG abnormality 2–4 h postdose. Highest dose of 100 mg/kg caused severe hypoglycemia with a mean GLU of
