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Drug Test Anal. 2019 Jan;11(1):68-76. doi: 10.1002/dta.2468. Epub 2018 Aug 14.

The pharmacokinetics of ketamine following intramuscular injection to F344 rats.

Author information

1
Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA.
2
KL Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, California, USA.
3
Biomedical Advanced Research and Development Authority (BARDA), Washington, District of Columbia, USA.

Abstract

Ketamine is a glutamate N-methyl-D-aspartate receptor antagonist that is a rapid-acting dissociative anesthetic. It has been proposed as an adjuvant treatment along with other drugs (atropine, midazolam, pralidoxime) used in the current standard of care (SOC) for organophosphate and nerve agent exposures. Ketamine is a pharmaceutical agent that is readily available to most clinicians in emergency departments and possesses a broad therapeutic index with well-characterized effects in humans. The objective of this study was to determine the pharmacokinetic profile of ketamine and its active metabolite, norketamine, in F344 rats following single or repeated intramuscular administrations of subanesthetic levels (7.5 mg/kg or 30 mg/kg) of ketamine with or without the SOC. Following administration, plasma and brain tissues were collected and analyzed using a liquid chromatography-mass spectrometry method to quantitate ketamine and norketamine. Following sample analysis, the pharmacokinetics were determined using non-compartmental analysis. The addition of the current SOC had a minimal impact on the pharmacokinetics of ketamine following intramuscular administration and repeated dosing at 7.5 mg/kg every 90 minutes allows for sustained plasma concentrations above 100 ng/mL. The pharmacokinetics of ketamine with and without the SOC in rats supports further investigation of the efficacy of ketamine co-administration with the SOC following nerve agent exposure in animal models.

KEYWORDS:

ketamine; liquid chromatography-mass spectrometry; nerve agent; norketamine; pharmacokinetics

PMID:
30027605
PMCID:
PMC6538562
[Available on 2020-01-01]
DOI:
10.1002/dta.2468
[Indexed for MEDLINE]

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