The pharmacokinetics of ketamine following intramuscular injection to F344 rats

Benjamin Moeller, Brenna Espelien, Waylon Weber, Philip Kuehl, Melanie Doyle-Eisele, C. Edwin Garner, Jacob D. McDonald, Efrain Garcia, Robert Raulli, Judith Laney

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
JournalDrug Testing and Analysis
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Pharmacokinetics
Intramuscular Injections
Inbred F344 Rats
Ketamine
Rats
Standard of Care
drug
plasma
anesthetic
organophosphate
Dissociative Anesthetics
spectrometry
brain
metabolite
Plasmas
Organophosphates
pharmacokinetics
Midazolam
Metabolites
N-Methyl-D-Aspartate Receptors

Keywords

  • ketamine
  • liquid chromatography–mass spectrometry
  • nerve agent
  • norketamine
  • pharmacokinetics

ASJC Scopus subject areas

  • Analytical Chemistry
  • Environmental Chemistry
  • Pharmaceutical Science
  • Spectroscopy

Cite this

Moeller, B., Espelien, B., Weber, W., Kuehl, P., Doyle-Eisele, M., Garner, C. E., ... Laney, J. (Accepted/In press). The pharmacokinetics of ketamine following intramuscular injection to F344 rats. Drug Testing and Analysis. https://doi.org/10.1002/dta.2468

The pharmacokinetics of ketamine following intramuscular injection to F344 rats. / Moeller, Benjamin; Espelien, Brenna; Weber, Waylon; Kuehl, Philip; Doyle-Eisele, Melanie; Garner, C. Edwin; McDonald, Jacob D.; Garcia, Efrain; Raulli, Robert; Laney, Judith.

In: Drug Testing and Analysis, 01.01.2018.

Research output: Contribution to journalArticle

Moeller, B, Espelien, B, Weber, W, Kuehl, P, Doyle-Eisele, M, Garner, CE, McDonald, JD, Garcia, E, Raulli, R & Laney, J 2018, 'The pharmacokinetics of ketamine following intramuscular injection to F344 rats', Drug Testing and Analysis. https://doi.org/10.1002/dta.2468
Moeller, Benjamin ; Espelien, Brenna ; Weber, Waylon ; Kuehl, Philip ; Doyle-Eisele, Melanie ; Garner, C. Edwin ; McDonald, Jacob D. ; Garcia, Efrain ; Raulli, Robert ; Laney, Judith. / The pharmacokinetics of ketamine following intramuscular injection to F344 rats. In: Drug Testing and Analysis. 2018.
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