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Pharmacokinetics, safety, and tolerability of oxfendazole in healthy volunteers: A randomized, placebo-controlled first-inhuman single-dose escalation study

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dc.contributor.author An, G.
dc.contributor.author Murry, D.J.
dc.contributor.author Gajurel, K.
dc.contributor.author Bach, T.
dc.contributor.author Deye, G.
dc.contributor.author Stebounova, L.V.
dc.contributor.author Codd, E.E.
dc.contributor.author Horton, J.
dc.contributor.author Gonzalez, A.E.
dc.contributor.author Garcia, H.H.
dc.contributor.author Ince, D.
dc.contributor.author Hodgson-Zingman, D.
dc.contributor.author Nomicos, E.Y.H.
dc.contributor.author Conrad, T.
dc.contributor.author Kennedy, J.
dc.contributor.author Jones, W.
dc.contributor.author Gilman, R.H.
dc.contributor.author Winokur, P.
dc.date.accessioned 2019-12-06T20:57:46Z
dc.date.available 2019-12-06T20:57:46Z
dc.date.issued 2019
dc.identifier.uri https://hdl.handle.net/20.500.12866/7396
dc.description.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 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. en_US
dc.language.iso eng
dc.publisher American Society for Microbiology
dc.relation.ispartof urn:issn:1098-6596
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject activated partial thromboplastin time en_US
dc.subject adult en_US
dc.subject Anthelmintic agent en_US
dc.subject area under the curve en_US
dc.subject arthralgia en_US
dc.subject Article en_US
dc.subject aspartate aminotransferase en_US
dc.subject bicarbonate en_US
dc.subject bicarbonate blood level en_US
dc.subject Clinical pharmacokinetics en_US
dc.subject controlled study en_US
dc.subject Cysticercosis en_US
dc.subject diarrhea en_US
dc.subject double blind procedure en_US
dc.subject drug bioavailability en_US
dc.subject drug dose escalation en_US
dc.subject drug dose regimen en_US
dc.subject drug exposure en_US
dc.subject drug metabolism en_US
dc.subject drug metabolite en_US
dc.subject drug safety en_US
dc.subject drug solubility en_US
dc.subject drug tolerability en_US
dc.subject elimination half-life en_US
dc.subject elimination rate constant en_US
dc.subject eosinophilia en_US
dc.subject female en_US
dc.subject fenbendazole en_US
dc.subject first in human study en_US
dc.subject First-in-human study en_US
dc.subject flatulence en_US
dc.subject human en_US
dc.subject intestine absorption en_US
dc.subject leukocytosis en_US
dc.subject leukopenia en_US
dc.subject limit of quantitation en_US
dc.subject liquid chromatography-mass spectrometry en_US
dc.subject major clinical study en_US
dc.subject male en_US
dc.subject maximum plasma concentration en_US
dc.subject neutropenia en_US
dc.subject no-observed-adverse-effect level en_US
dc.subject normal human en_US
dc.subject oxfendazole en_US
dc.subject Oxfendazole en_US
dc.subject oxfendazole glucuronide en_US
dc.subject oxfendazole sulfate en_US
dc.subject oxfendazole sulfone en_US
dc.subject pharmacokinetic parameters en_US
dc.subject phase 1 clinical trial en_US
dc.subject plasma concentration-time curve en_US
dc.subject plasma half life en_US
dc.subject PR interval en_US
dc.subject priority journal en_US
dc.subject randomized controlled trial en_US
dc.subject renal clearance en_US
dc.subject side effect en_US
dc.subject single drug dose en_US
dc.subject sore throat en_US
dc.subject time to maximum plasma concentration en_US
dc.subject ultra performance liquid chromatography en_US
dc.subject unclassified drug en_US
dc.subject urinary excretion en_US
dc.subject viral gastroenteritis en_US
dc.subject volume of distribution en_US
dc.title Pharmacokinetics, safety, and tolerability of oxfendazole in healthy volunteers: A randomized, placebo-controlled first-inhuman single-dose escalation study en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1128/AAC.02255-18
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.00 es_PE
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.03.08
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.01.05


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