Print Email Facebook Twitter Pharmacokinetics and efficacy of atropine sulfate/obidoxime chloride co-formulation against VX in a guinea pig model Title Pharmacokinetics and efficacy of atropine sulfate/obidoxime chloride co-formulation against VX in a guinea pig model Author Kentrop, J. Savransky, V. Klaassen, S.D. van Groningen, T. Bohnert, S. Cornelissen, A.S. Cochrane, L. Barry, J. Joosen, M.J.A. Publication year 2021 Abstract Nerve agent exposure is generally treated by an antidote formulation composed of a muscarinic antagonist, atropine sulfate (ATR), and a reactivator of acetylcholinesterase (AChE) such as pralidoxime, obidoxime (OBI), methoxime, trimedoxime or HI-6 and an anticonvulsant. Organophosphates (OPs) irreversibly inhibit AChE, the enzyme responsible for termination of acetylcholine signal transduction. Inhibition of AChE leads to overstimulation of the central and peripheral nervous system with convulsive seizures, respiratory distress and death as result. The present study evaluated the efficacy and pharmacokinetics (PK) of ATR/OBI following exposure to two different VX dose levels. The PK of ATR and OBI administered either as a single drug, combined treatment but separately injected, or administered as the ATR/OBI co-formulation, was determined in plasma of naïve guinea pigs and found to be similar for all formulations. Following subcutaneous VX exposure, ATR/OBI-treated animals showed significant improvement in survival rate and progression of clinical signs compared to untreated animals. Moreover, AChE activity after VX exposure in both blood and brain tissue was significantly higher in ATR/OBI-treated animals compared to vehicle-treated control. In conclusion, ATR/OBI has been proven to be efficacious against exposure to VX and there were no PK interactions between ATR and OBI when administered as a co-formulation. Subject Atropine sulfateObidoxime chloridePharmacokineticsGuinea pigNerve agentsDefence ResearchDefence, Safety and Security To reference this document use: http://resolver.tudelft.nl/uuid:ce043302-9b28-441e-8619-2c21fdc0edfa TNO identifier 884041 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.