Pharmacokinetics, Safety, and Tolerability of Oxfendazole in Healthy Adults in an Open-Label Phase 1 Multiple Ascending Dose and Food Effect Study

Thanh Bach, Shirley Galbiati, Jessie K. Kennedy, Gregory Deye, Effie Y.H. Nomicos, Ellen E. Codd, Hector H. Garcia, John Horton, Robert H. Gilman, Armando E. Gonzalez, Patricia Winokur, Guohua An

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Neurocysticercosis and trichuriasis are difficult-to-treat parasitic infections that affect more than 1.5 billion people worldwide. Oxfendazole, a potent broad-spectrum benzimidazole anthelmintic approved for use in veterinary medicine, has shown substantial antiparasitic activity against neurocysticercosis and intestinal helminths in preclinical studies. As part of a program to transition oxfendazole from veterinary medicine to human use, phase I multiple ascending dose and food effect studies were conducted. Thirty-six healthy adults were enrolled in an open-label study which evaluated (i) the pharmacokinetics and safety of oxfendazole following multiple ascending doses of oxfendazole oral suspension at 3, 7.5, and 15 mg/kg once daily for 5 days and (ii) the effect of food on oxfendazole pharmacokinetics and safety after a single 3-mg/kg dose administered following an overnight fast or the consumption of a fatty breakfast. Following multiple oral dose administration, the intestinal absorption of oxfendazole was rapid, with the time to maximum concentration of drug in serum (Tmax) ranging from 1.92 to 2.56 h. A similar half-life of oxfendazole (9.21 to 11.8 h) was observed across all dose groups evaluated, and oxfendazole exhibited significantly less than a dose-proportional increase in exposure. Oxfendazole plasma exposures were higher in female subjects than in male subjects. Following daily administration, oxfendazole reached a steady state in plasma on study day 3, with minimal accumulation. Food delayed the oxfendazole Tmax by a median of 6.88 h and resulted in a 49.2% increase in the maximum observed drug concentration in plasma (Cmax) and an 86.4% increase in the area under the concentration-time curve (AUC). Oxfendazole was well tolerated in all study groups, and there were no major safety signals identified in this study. (This study has been registered at ClinicalTrials.gov under identifier NCT03035760.

Original languageEnglish
Article numbere01018
JournalAntimicrobial Agents and Chemotherapy
Volume64
Issue number11
DOIs
StatePublished - Oct 2020

Bibliographical note

Funding Information:
This work was supported by the Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, through the Vaccine and Treatment Evaluation Unit (contract no. HHSN272200800008C and contract no. HHSN272201300020I) and by a National Center for Advancing Translational Sciences grant to the University of Iowa (grant no. 5U54TR001356) for the work done in the Clinical Research Unit.

Publisher Copyright:
Copyright © 2020 American Society for Microbiology. All Rights Reserved.

Keywords

  • Clinical pharmacokinetics
  • Food effect
  • Oxfendazole
  • Soil-transmitted helminthiasis

Fingerprint

Dive into the research topics of 'Pharmacokinetics, Safety, and Tolerability of Oxfendazole in Healthy Adults in an Open-Label Phase 1 Multiple Ascending Dose and Food Effect Study'. Together they form a unique fingerprint.

Cite this