Pharmacokinetics of midazolam and its major metabolite 1-hydroxymidazolam in the ball python (Python regius) after intracardiac and intramuscular administrations.

Abstract

Midazolam is a benzodiazepine with sedative, muscle relaxant, anxiolytic, and anticonvulsant effects. Twelve ball pythons (Python regius) were used in a parallel study evaluating the pharmacokinetics of 1mg/kg midazolam following a single intracardiac (IC) or intramuscular (IM) administration. Blood was collected from a central venous catheter placed 7days prior, or by cardiocentesis, at 15 time points starting just prior to and up to 72hr after drug administration. Plasma concentrations of midazolam and 1-hydroxymidazolam were determined by the use of high-performance liquid chromatography tandem-mass spectrometry and pharmacokinetic parameters were estimated using noncompartmental analysis. The mean±SD terminal half-lives of IC and IM midazolam were 12.04±3.25hr and 16.54±7.10hr, respectively. The area under the concentration-time curve extrapolated to infinity, clearance, and apparent volume of distribution in steady-state of IC midazolam were 19,112.3±3,095.9ng*hr/ml, 0.053±0.008 Lhr-1 kg-1 , and 0.865±0.289L/kg, respectively. The bioavailability of IM midazolam was estimated at 89%. Maximum plasma concentrations following an IM administration were reached 2.33±0.98hr and 24.00±14.12hr postinjection for midazolam and 1-hydroxymidazolam, respectively, and 22.33±20.26hr postinjection for 1-hydroxymidazolam following IC administration.