PMID- 30745383
OWN - NLM
STAT- MEDLINE
DCOM- 20200226
LR  - 20200309
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 63
IP  - 4
DP  - 2019 Apr
TI  - Pharmacokinetics, Safety, and Tolerability of Oxfendazole in Healthy Volunteers: 
      a Randomized, Placebo-Controlled First-in-Human Single-Dose Escalation Study.
LID - 10.1128/AAC.02255-18 [doi]
LID - e02255-18
AB  - 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 Taenia solium 
      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.).
CI  - Copyright (c) 2019 American Society for Microbiology.
FAU - An, Guohua
AU  - An G
AD  - Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, 
      University of Iowa, Iowa City, Iowa, USA guohua-an@uiowa.edu 
      patricia-winokur@uiowa.edu.
FAU - Murry, Daryl J
AU  - Murry DJ
AD  - Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, 
      University of Iowa, Iowa City, Iowa, USA.
FAU - Gajurel, Kiran
AU  - Gajurel K
AD  - Division of Infectious Diseases, Carver College of Medicine, University of Iowa, 
      Iowa City, Iowa, USA.
FAU - Bach, Thanh
AU  - Bach T
AD  - Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, 
      University of Iowa, Iowa City, Iowa, USA.
FAU - Deye, Greg
AU  - Deye G
AD  - Division of Microbiology and Infectious Diseases, National Institute of Allergy 
      and Infectious Diseases, Bethesda, Maryland, USA.
FAU - Stebounova, Larissa V
AU  - Stebounova LV
AD  - Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, 
      University of Iowa, Iowa City, Iowa, USA.
FAU - Codd, Ellen E
AU  - Codd EE
AD  - Codd Consulting, LLC, Blue Bell, Pennsylvania, USA.
AD  - Oxfendazole Development Group, Blue Bell, Pennsylvania, USA.
FAU - Horton, John
AU  - Horton J
AD  - Tropical Projects, Hitchin, United Kingdom.
AD  - Oxfendazole Development Group, Blue Bell, Pennsylvania, USA.
FAU - Gonzalez, Armando E
AU  - Gonzalez AE
AD  - School of Veterinary Medicine, Universidual Nacional Mayor de San Marcos, Lima, 
      Peru.
AD  - Oxfendazole Development Group, Blue Bell, Pennsylvania, USA.
AD  - Center for Global Health, Universidad Peruana Cayetano Heredia, Lima, Peru.
FAU - Garcia, Hector H
AU  - Garcia HH
AD  - Center for Global Health, Universidad Peruana Cayetano Heredia, Lima, Peru.
AD  - Oxfendazole Development Group, Blue Bell, Pennsylvania, USA.
FAU - Ince, Dilek
AU  - Ince D
AD  - Division of Infectious Diseases, Carver College of Medicine, University of Iowa, 
      Iowa City, Iowa, USA.
FAU - Hodgson-Zingman, Denice
AU  - Hodgson-Zingman D
AD  - Division of Cardiology, Carver College of Medicine, University of Iowa, Iowa 
      City, Iowa, USA.
FAU - Nomicos, Effie Y H
AU  - Nomicos EYH
AD  - Division of Microbiology and Infectious Diseases, National Institute of Allergy 
      and Infectious Diseases, Bethesda, Maryland, USA.
FAU - Conrad, Thomas
AU  - Conrad T
AD  - The Emmes Corporation, Rockville, Maryland, USA.
FAU - Kennedy, Jessie
AU  - Kennedy J
AD  - The Emmes Corporation, Rockville, Maryland, USA.
FAU - Jones, Walt
AU  - Jones W
AD  - Division of Microbiology and Infectious Diseases, National Institute of Allergy 
      and Infectious Diseases, Bethesda, Maryland, USA.
FAU - Gilman, Robert H
AU  - Gilman RH
AD  - Johns Hopkins School of Public Health, Johns Hopkins University, Baltimore, 
      Maryland, USA.
AD  - Oxfendazole Development Group, Blue Bell, Pennsylvania, USA.
FAU - Winokur, Patricia
AU  - Winokur P
AD  - Division of Infectious Diseases, Carver College of Medicine, University of Iowa, 
      Iowa City, Iowa, USA guohua-an@uiowa.edu patricia-winokur@uiowa.edu.
LA  - eng
SI  - ClinicalTrials.gov/NCT02234570
GR  - HHSN272200800008C/AI/NIAID NIH HHS/United States
GR  - HHSN272201300020I/AI/NIAID NIH HHS/United States
GR  - U54 TR001356/TR/NCATS NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
DEP - 20190327
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Benzimidazoles)
RN  - E24GX49LD8 (benzimidazole)
RN  - OMP2H17F9E (oxfendazole)
SB  - IM
MH  - Administration, Oral
MH  - Adolescent
MH  - Adult
MH  - Benzimidazoles/*pharmacokinetics
MH  - Biological Availability
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Half-Life
MH  - Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Young Adult
PMC - PMC6437481
OTO - NOTNLM
OT  - anthelmintic agent
OT  - clinical pharmacokinetics
OT  - cysticercosis
OT  - first-in-human study
OT  - oxfendazole
EDAT- 2019/02/13 06:00
MHDA- 2020/02/27 06:00
PMCR- 2019/09/27
CRDT- 2019/02/13 06:00
PHST- 2018/10/27 00:00 [received]
PHST- 2019/02/01 00:00 [accepted]
PHST- 2019/02/13 06:00 [pubmed]
PHST- 2020/02/27 06:00 [medline]
PHST- 2019/02/13 06:00 [entrez]
PHST- 2019/09/27 00:00 [pmc-release]
AID - AAC.02255-18 [pii]
AID - 02255-18 [pii]
AID - 10.1128/AAC.02255-18 [doi]
PST - epublish
SO  - Antimicrob Agents Chemother. 2019 Mar 27;63(4):e02255-18. doi: 
      10.1128/AAC.02255-18. Print 2019 Apr.