Journal article
Pharmacokinetics, Safety, and Tolerability of Oxfendazole in Healthy Volunteers: a Randomized, Placebo-Controlled First-in-Human Single-Dose Escalation Study
Antimicrobial agents and chemotherapy, Vol.63(4), e02255-18
04/2019
DOI: 10.1128/AAC.02255-18
PMCID: PMC6437481
PMID: 30745383
Abstract
Cysticercosis is a parasitic disease that frequently involves the human central nervous system (CNS), and current treatment options are limited. Oxfendazole, a veterinary medicine belonging to the benzimidazole family of anthelmintic drugs, has demonstrated substantial activity against the tissue stages of
and has potential to be developed as an effective therapy for neurocysticercosis. To accelerate the transition of oxfendazole from veterinary to human use, the pharmacokinetics, safety, and tolerability of oxfendazole were evaluated in healthy volunteers in this phase 1 first-in-human (FIH) study. Seventy subjects were randomly assigned to receive a single oral dose of oxfendazole (0.5, 1, 3, 7.5, 15, 30, or 60 mg oxfendazole/kg body weight) or placebo and were followed for 14 days. Blood and urine samples were collected, and the concentrations of oxfendazole were measured using a validated ultraperformance liquid chromatography mass spectrometry method. The pharmacokinetic parameters of oxfendazole were estimated using noncompartmental analysis. Oxfendazole was rapidly absorbed with a mean plasma half-life ranging from 8.5 to 11 h. The renal excretion of oxfendazole was minimal. Oxfendazole exhibited significant nonlinear pharmacokinetics with less than dose-proportional increases in exposure after single oral doses of 0.5 mg/kg to 60 mg/kg. This nonlinearity of oxfendazole is likely due to the dose-dependent decrease in bioavailability that is caused by its low solubility. Oxfendazole was found to be well tolerated in this study at different escalating doses without any serious adverse events (AEs) or deaths. There were no significant differences in the distributions of hematology, biochemistry, or urine parameters between oxfendazole and placebo recipients. (This study has been registered at ClinicalTrials.gov under identifier NCT02234570.).
Details
- Title: Subtitle
- Pharmacokinetics, Safety, and Tolerability of Oxfendazole in Healthy Volunteers: a Randomized, Placebo-Controlled First-in-Human Single-Dose Escalation Study
- Creators
- Guohua An - Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa, USA guohua-an@uiowa.edu patricia-winokur@uiowa.eduDaryl J Murry - Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa, USAKiran Gajurel - Division of Infectious Diseases, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USAThanh Bach - Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa, USAGreg Deye - Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USALarissa V Stebounova - Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa, USAEllen E Codd - Oxfendazole Development Group, Blue Bell, Pennsylvania, USAJohn Horton - Oxfendazole Development Group, Blue Bell, Pennsylvania, USAArmando E Gonzalez - Center for Global Health, Universidad Peruana Cayetano Heredia, Lima, PeruHector H Garcia - Oxfendazole Development Group, Blue Bell, Pennsylvania, USADilek Ince - Division of Infectious Diseases, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USADenice Hodgson-Zingman - Division of Cardiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USAEffie Y H Nomicos - Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USAThomas Conrad - The Emmes Corporation, Rockville, Maryland, USAJessie Kennedy - The Emmes Corporation, Rockville, Maryland, USAWalt Jones - Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USARobert H Gilman - Oxfendazole Development Group, Blue Bell, Pennsylvania, USAPatricia Winokur - Division of Infectious Diseases, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA guohua-an@uiowa.edu patricia-winokur@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Antimicrobial agents and chemotherapy, Vol.63(4), e02255-18
- DOI
- 10.1128/AAC.02255-18
- PMID
- 30745383
- PMCID
- PMC6437481
- ISSN
- 0066-4804
- eISSN
- 1098-6596
- Grant note
- U54 TR001356 / NCATS NIH HHS HHSN272200800008C / NIAID NIH HHS HHSN272201300020I / NIAID NIH HHS
- Language
- English
- Date published
- 04/2019
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Infectious Diseases; Pharmaceutical Sciences and Experimental Therapeutics; Cardiovascular Medicine; Medicine Administration; Holden Comprehensive Cancer Center; Internal Medicine
- Record Identifier
- 9984094552602771
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