Freeze-dried Equine-derived Redback Spider Antivenom: a Local Irritation Study by Intramuscular Injection in Rabbits and a Repeated-dose Toxicity Study in Rats

Overview

Journal J Toxicol Pathol

Date 2018 May 12

PMID 29749999

Authors

Akihiko Yamamoto

Satomi Harano

Noriko Shinya

Ayataka Nagano

Yoshinobu Miyatsu

Kyouko Sawabe

Takayuki Matsumura

Manabu Ato

Motohide Takahashi

Hisashi Taki

Toru Hifumi

Affiliations

Soon will be listed here.

Abstract

The redback spider () is nonindigenous to Japan but has now spread throughout the country. Bites to humans are rare but can be fatal. We prepared freeze-dried redback spider antivenom for therapeutic use against bites in Japan by immunization of horse plasma. This study included two nonclinical tests of the antivenom: a local irritation study involving a single intramuscular administration to rabbits (with injections of physiological saline and an existing freeze-dried diphtheria antitoxin as control and comparison substances, respectively) and a 2-week repeated intermittent intravenous-dose toxicity study in rats. The irritation study showed the antivenom's irritancy to be comparable with that of the saline and the existing antitoxin preparations under the test conditions. In a repeated-dose toxicity study, no toxicity change was found in male or female rats, and the no-observed-adverse-effect level (NOAEL) was judged to be a dose volume of 20 mL/kg (1082 units/kg antivenom activity) in both male and female rats. In addition, there was no toxicological difference between proteinaceous diphtheria antitoxin and redback spider antivenom prepared to have the same protein content and the same additive composition. Based on these findings, we will further advance our research towards clinical application of the redback spider antivenom. This research was supported by the Research Program on Emerging and Re-emerging Infectious Disease of the Japan Agency for Medical Research and Development.

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