Pharmacokinetics and pharmacodynamics of dextroketamine alone or combined with midazolam in Caiman crocodilus

Abstract

Pharmacokinetics studies of anesthetic agents are important for understanding of the pharmacology and metabolism of anesthetic agents in reptilians. This study was designed to examine the pharmacokinetic and pharmacodynamic properties of intravenous dextroketamine alone or combined with midazolam in Caiman crocodilus. Eight caimans were anesthetized with dextroketamine (10 mg/kg; group D) or dextroketamine and midazolam (10 and 0.5 mg/kg respectively; group DM) into the occipital venous sinus. The pharmacokinetic parameters were calculated by HPLC using a non-compartmental modeling. Serial blood samples were collected at baseline and within 15 and 30 min, and 11.5, 2, 4, 8, 12, 24 and 48 h of drug administration. Sedation status over time differed between groups. All animals in group D (8/8; 100%) showed signs of light sedation at t10. Half (4/8; 50%) of these caimans did not progress to deeper levels of sedation. In spite of light sedation at t10, animals in group DM were deeply sedated within 13.13 ± 7.04 min of anesthetic agent injection. The area under the plasma concentration–time curve (AUC_0–48) and half-life of dextroketamine changed significantly after combination with midazolam. Even without significant changes in clearance, the almost two-fold increase in the half-life of dextroketamine suggests a slower rate of elimination.