Intramuscular diazepam pharmacokinetics in soman-exposed guinea pigs

Journal of Applied Toxicology : JAT
B R CapacioJ H McDonough

Abstract

Intramuscular (i.m.) diazepam is included by the US military as an anticonvulsant in the standard therapeutic regimen for organophosphorus nerve agent intoxication. In this study we investigated the pharmacokinetics of diazepam after i.m. administration while monitoring pharmacodynamic (electroencephalogram, EEG) data in soman-exposed guinea pigs. Prior to experiments the animals were surgically implanted with EEG leads to monitor seizure activity. For the study, animals were administered pyridostigmine (0.026 mg x kg(-1) i.m.) 30 min prior to soman (56 microg x kg(-1), 2 x LD50; subcutaneously, s.c.), which was followed in 1 min by atropine sulfate (2 mg x kg(-1) i.m.) and pralidoxime chloride (25 mg x kg(-1) i.m.). All animals receiving this regimen developed seizure activity. Diazepam (10 mg x kg(-1) i.m.) was administered 5 min after onset of seizure activity. Based on EEG data, animals were categorized as either seizure terminated or not terminated at 30 min after diazepam. Serial blood samples were obtained from each animal. Diazepam (10 mg x kg(-1) i.m.) terminated seizure activity in 52% of the animals within 30 min. The pharmacokinetics were characterized by a one-compartment model with first-order absorption and elimi...Continue Reading

References

May 1, 1979·The Journal of Pharmacy and Pharmacology·P DirnhuberJ A Stratton
Jan 1, 1978·Toxicology and Applied Pharmacology·J J GordonM P Maidment
Jan 1, 1992·Pharmacology, Biochemistry, and Behavior·C A CastroS B McMaster
Oct 1, 1991·Journal of Pharmaceutical Sciences·B J LukeyR P Solana
Aug 1, 1990·Journal of the Neurological Sciences·I J HaywardJ B Nold
Aug 1, 1989·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·J H McDonoughH E Modrow
Dec 1, 1985·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·C G McLeod
Dec 1, 1985·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·L LeadbeaterJ M Rylands
May 1, 1972·Electroencephalography and Clinical Neurophysiology·J A Lipp
Mar 1, 1981·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·J M Petras
Jan 1, 1993·Neuroscience and Biobehavioral Reviews·J H McDonough, T M Shih
Aug 1, 1997·Drug and Chemical Toxicology·B R CapacioB J Benton

❮ Previous
Next ❯

Citations

Apr 15, 2003·Toxicology and Applied Pharmacology·Tsung-Ming ShihJohn H McDonough
Mar 20, 2003·Drug and Chemical Toxicology·B R CapacioJ H McDonough
Jun 17, 2004·Drug and Chemical Toxicology·Benedict R CapacioJ H McDonough
Nov 25, 2003·Pharmacology & Toxicology·Miroslav M SavićDubravko R Bokonjić
Jul 17, 2010·Journal of Applied Toxicology : JAT·Victor A VoicuDalia Simona Miron
Jul 12, 2005·Journal of Pharmacological and Toxicological Methods·John P PattersonAlan S Bass
Apr 22, 2003·Annual Review of Biomedical Engineering·Alan J RussellRichard R Koepsel
Mar 20, 2004·The Journal of Pharmacology and Experimental Therapeutics·Patrick K HarrisonJohn E H Tattersall

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.