Pharmacokinetics of ketamine in the horse.

The research focused on understanding the behavior of ketamine, a common anesthetic, in horses. The study developed a pharmacokinetic model based on ketamine plasma concentration data, revealing average distribution and elimination phase half-lives, volume of central and peripheral compartments, total body clearance rate, plasma protein binding, and duration of anesthesia from a specific dose.

Pharmacokinetic Model Development

• The researchers gave an intravenous dose of ketamine hydrochloride (HCl) to horses who were also given another medication called xylazine HCl. They measured the plasma concentration of ketamine multiple times after administering the drug to understand its distribution in the horse’s body. These measurements were used to create a two-compartment pharmacokinetic model, which is a mathematical model that describes the way a drug is absorbed, distributed, metabolized and excreted in the body.

Distribution and Elimination Phase Half-Lives

• Half-life is the time necessary for the concentration of the drug reduced by half in the body. The study found that average distribution phase half-life was 2.9 minutes. It meant that the concentration of ketamine in horse’s body decreased by half during distribution in just under 3 minutes.
• The elimination phase half-life of ketamine was found to be significantly longer, averaging at 42 minutes. This indicates that it took approximately 42 minutes for the concentration of the drug to reduce by half during the elimination phase, which is when the body is getting rid of the drug.

Volume of Central and Peripheral Compartments

• The central compartment volume averaged at 212 ml/kg of body weight. This involves highly perfused organs such as the heart, liver, and kidneys, where the drug mainly distributes after being administered.
• The volume of the peripheral compartment, which is less perfused tissues like muscle and fat, was approximately three times larger than that of the central compartment. This indicates that a considerable proportion of the administrated ketamine dose was available in these less perfused tissues.

Total Body Clearance and Plasma Protein Binding

• The total body clearance of ketamine averaged at 26.6 ml/minute/kg. This means the horse’s body could clear around 26.6 ml of the drug per minute for each kilogram of the horse’s weight.
• About 50% of the ketamine was binded with plasma proteins. Plasma protein binding is a crucial factor in pharmacokinetics because it affects the drug’s distribution and elimination.

Duration of Anesthesia

• The study observed the effect and duration of anesthesia from a single intravenous bolus dose of 2.2 mg/kg of ketamine HCl. A consistent observation was that the duration of anesthesia was determined largely by distribution. This means that once the drug was distributed in the organs and tissues, the anesthesia effect kicked in and lasted for a defined duration.
• Moreover, the model suggests that at the time of recovery from anesthesia, approximately 40% of the initial ketamine dose remained in the horse’s body.