Pharmacokinetics and metabolism of intravenous doxapram in horses.

The research examines how doxapram, a drug administered to horses, is absorbed, distributed, metabolized, and excreted from the body, while also determining its physical effects on horses of varying weights and dosages.

Research Detail

The study explores the pharmacokinetics and metabolism of Doxapram in horses. Pharmacokinetics deals with how a drug is absorbed, distributed, metabolized, and excreted in the body. Thus, the research offers important insights into the processing of Doxapram by equine organisms.

• Doxapram was administered intravenously to the horses in doses of 0.275, 0.55, and 1.1 mg/kg body weight.
• Plasma concentrations of the drug decreased rapidly following administration. This means that the body was quickly processing and removing the drug from the bloodstream.
• The research found that the rate at which the drug was cleared from the body was largely consistent across all three doses, with median values of total body clearance being 10.9, 10.6, and 10.9 ml/min/kg respectively.
• The drug was distributed throughout the body, showing a steady-state volume of distribution of around 1,200 ml/kg.
• The half-life of the drug, the time it takes for the amount of drug in the body to be cut by half, ranged from 121 to 178 mins.

Binding and Elimination

Doxapram activity was also evaluated in terms of its protein binding characteristics and its elimination routes:

• Protein binding determines how long a drug remains in the body; in this case, it ranged from 76 to 85.4 per cent, which is relatively high.
• The blood-to-plasma concentration ratio of the drug was around 0.8, which indicates a high level of drug permeability across the blood-brain-barrier (BBB).
• The renal clearance or elimination of the drug via the kidneys was found to be a minor route of elimination, indicating that the drug is not majorly excreted through urine.
• On the other hand, the metabolic clearance of Doxapram was found to be a major route of elimination, suggesting that the drug is primarily processed and removed by the liver.

Metabolites and Effect

The study also identified four metabolites resulted when the drug was broken down:

• It was found that the rapid disappearance of Doxapram from plasma was due to the redistribution of the drug from the plasma to other tissues. This redistribution also accounts for the short duration of the clinical effect of the drug.
• However, it was also noted that continuous or repeated administration of doxapram could prolong the duration of its clinical effect, as re-distribution would become less important as body reaches a steady-state with these conditions.