Pharmacokinetics of midazolam in sevoflurane-anesthetized cats

Urshulaa Dholakia, Reza Seddighi, Sherry K. Cox, Xiaocun Sun, Bruno H. Pypendop

Research output: Contribution to journalArticle

Abstract

Objective: To estimate the pharmacokinetics of midazolam and 1-hydroxymidazolam after midazolam administration as an intravenous bolus in sevoflurane-anesthetized cats. Study design: Prospective pharmacokinetic study. Animals: A group of six healthy adult, female domestic cats. Methods: Anesthesia was induced and maintained with sevoflurane. After 30 minutes of anesthetic equilibration, cats were administered midazolam (0.3 mg kg–1) over 15 seconds. Venous blood was collected at 0, 1, 2, 4, 8, 15, 30, 45, 90, 180 and 360 minutes after administration. Plasma concentrations for midazolam and 1-hydroxymidazolam were measured using high-pressure liquid chromatography. The heart rate (HR), respiratory rate (fR), rectal temperature, noninvasive mean arterial pressure (MAP) and end-tidal carbon dioxide (PE′CO2) were recorded at 5 minute intervals. Population compartment models were fitted to the time–plasma midazolam and 1-hydroxymidazolam concentrations using nonlinear mixed effect modeling. Results: The pharmacokinetic model was fitted to the data from five cats, as 1-hydroxymidazolam was not detected in one cat. A five-compartment model best fitted the data. Typical values (% interindividual variability where estimated) for the volumes of distribution for midazolam (three compartments) and hydroxymidazolam (two compartments) were 117 (14), 286 (10), 705 (14), 53 (36) and 334 mL kg–1, respectively. Midazolam clearance to 1-hydroxymidazolam, midazolam fast and slow intercompartmental clearances, 1-hydroxymidazolam clearance and 1-hydroxymidazolam intercompartment clearance were 18.3, 63.5 (15), 22.1 (8), 1.7 (67) and 3.8 mL minute–1 kg–1, respectively. No significant changes in HR, MAP, fR or PE′CO2 were observed following midazolam administration. Conclusion and clinical relevance: In sevoflurane-anesthetized cats, a five-compartment model best fitted the midazolam pharamacokinetic profile. There was a high interindividual variability in the plasma 1-hydroxymidazolam concentrations, and this metabolite had a low clearance and persisted in the plasma for longer than the parent drug. Midazolam administration did not result in clinically significant changes in physiologic variables.

Original languageEnglish (US)
Pages (from-to)200-209
Number of pages10
JournalVeterinary Anaesthesia and Analgesia
Volume47
Issue number2
DOIs
StatePublished - Mar 2020

Keywords

  • 1-hydroxymidazolam
  • cat anesthesia
  • midazolam
  • pharmacokinetics
  • sevoflurane

ASJC Scopus subject areas

  • veterinary(all)

Fingerprint Dive into the research topics of 'Pharmacokinetics of midazolam in sevoflurane-anesthetized cats'. Together they form a unique fingerprint.

  • Cite this