In vivo analysis of the effects of intravenously as well as orally administered moxifloxacin on the pharmacokinetic and electrocardiographic variables along with its torsadogenic action in the chronic atrioventricular block cynomolgus monkeys

• Main Authors: Ai Goto (Author), Kengo Sakamoto (Author), Mihoko Hagiwara-Nagasawa (Author), Ryuichi Kambayashi (Author), Koki Chiba (Author), Yoshio Nunoi (Author), Hiroko Izumi-Nakaseko (Author), Yoshinori Takei (Author), Akio Matsumoto (Author), Atsushi Sugiyama (Author)
• Format: Book
• Published: Elsevier, 2020-08-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

We analyzed the effects of intravenously as well as orally administered moxifloxacin on the pharmacokinetic and electrocardiographic variables along with its torsadogenic action using the chronic atrioventricular block cynomolgus monkeys with a cross-over design. Initially, moxifloxacin was intravenously administered in doses of 60 mg/kg/2 h, 60 mg/kg/1 h and 105 mg/kg/1.75 h with an interval of >1 week (n = 3), which provided Cmax of 19.7, 25.4 and 37.8 μg/mL, and induced torsade de pointes in 1, 0 and 3 out of 3 animals, respectively. Next, moxifloxacin was orally administered in doses of 10, 30 and 100 mg/kg with an interval of >1 week (n = 6), which provided Cmax of 1.8, 4.2 and 8.9 μg/mL, and induced torsade de pointes in 0, 0 and 2 out of 6 animals, respectively. A close analysis of pharmacokinetic and electrocardiographic variables indicates that torsade de pointes was induced in animals that had experienced larger systemic exposure of moxifloxacin and/or greater peak QTcF, although Cmax by itself did not necessarily reflect the incidence of torsade de pointes when its administration route was different. These findings may provide a basic guide how to use moxifloxacin in safe for patients with labile repolarization process.

Item Description

1347-8613
10.1016/j.jphs.2020.05.006