Preclinical studies on the pharmacokinetics, safety, and toxicology of oxfendazole: Toward first in human studies

Ellen E. Codd; Hanna H. Ng; Claire McFarlane; Edward S. Riccio; Rupa Doppalapudi; Jon C. Mirsalis; R. John Horton; Armando E. Gonzalez; H. Hugo Garcia; Robert H. Gilman

doi:10.1177/1091581815569582

Preclinical studies on the pharmacokinetics, safety, and toxicology of oxfendazole: Toward first in human studies

Ellen E. Codd, Hanna H. Ng, Claire McFarlane, Edward S. Riccio, Rupa Doppalapudi, Jon C. Mirsalis, R. John Horton, Armando E. Gonzalez, H. Hugo Garcia, Robert H. Gilman

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

A 2-week study in rats identified target organs of oxfendazole toxicity to be bone marrow, epididymis, liver, spleen, testis, and thymus. Female rats had greater oxfendazole exposure and exhibited toxicities at lower doses than did males. Decreased white blood cell levels, a class effect of benzimidazole anthelmintics, returned to normal during the recovery period. The no observed adverse effect level was determined to be >5 but <25 mg/kg/d and the maximum tolerated dose 100 mg/kg/d. The highest dose, 200 mg/kg/d, resulted in significant toxicity and mortality, leading to euthanization of the main study animals in this group after 7 days. Oxfendazole did not exhibit genetic toxicology signals in standard Ames bacterial, mouse lymphoma, or rat micronucleus assays nor did it provoke safety concerns when evaluated for behavioral effects in rats or cardiovascular safety effects in dogs. These results support the transition of oxfendazole to First in Human safety studies preliminary to its evaluation in human helminth diseases.

Original language	English
Pages (from-to)	129-137
Number of pages	9
Journal	International Journal of Toxicology
Volume	34
Issue number	2
DOIs	https://doi.org/10.1177/1091581815569582
State	Published - 10 Mar 2015

Bibliographical note

Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN266200600011C / N01-AI-60011. HHG is supported by a Wellcome Trust Senior International Research Fellowship in Public Health and Tropical Medicine.

Publisher Copyright:
© The Author(s) 2015.

Keywords

anthelmintic
benzimidazole
cysticercosis
soil-transmitted helminths

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title = "Preclinical studies on the pharmacokinetics, safety, and toxicology of oxfendazole: Toward first in human studies",

abstract = "A 2-week study in rats identified target organs of oxfendazole toxicity to be bone marrow, epididymis, liver, spleen, testis, and thymus. Female rats had greater oxfendazole exposure and exhibited toxicities at lower doses than did males. Decreased white blood cell levels, a class effect of benzimidazole anthelmintics, returned to normal during the recovery period. The no observed adverse effect level was determined to be >5 but <25 mg/kg/d and the maximum tolerated dose 100 mg/kg/d. The highest dose, 200 mg/kg/d, resulted in significant toxicity and mortality, leading to euthanization of the main study animals in this group after 7 days. Oxfendazole did not exhibit genetic toxicology signals in standard Ames bacterial, mouse lymphoma, or rat micronucleus assays nor did it provoke safety concerns when evaluated for behavioral effects in rats or cardiovascular safety effects in dogs. These results support the transition of oxfendazole to First in Human safety studies preliminary to its evaluation in human helminth diseases.",

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Preclinical studies on the pharmacokinetics, safety, and toxicology of oxfendazole: Toward first in human studies

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Keywords

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