Pharmacokinetics and pharmacodynamics of the injectable formulation of methadone hydrochloride and methadone in lipid nanocarriers administered orally to horses.

This research investigated the effects and pharmacokinetics of the injectable formulation or nanoparticulated methadone given orally in horses. The study concluded that neither form produced antinociception and the nanoparticulated form did not improve methadone pharmacokinetics or increase systemic body exposure to methadone.

Methodology and Objectives

• The research was conducted on six adult mares using a blind and prospective design with crossover.
• The objectives were to understand the thermal, electrical, and mechanical antinociceptive and other physiological effects like heart rate, respiratory rate, blood pressure etc. It also sought to study the pharmacokinetic behavior of the drug when given orally in two forms – the injectable formulation (ORAL) or nanoparticulated (NANO) methadone.

Experimental Analysis and Results

• The researchers used various statistical methods like repeated-measure models, Tukey’s test, and Wilcoxon signed-rank test, adjusted by Bonferroni tests to analyze the data they collected.
• They also collected blood samples from the horses for up to six hours after administering the doses to quantify the amount of drug in the blood plasma. This allowed them to study the pharmacokinetics based on noncompartmental and compartmental approaches.
• The results showed no difference in the pharmacodynamic parameters and most of the pharmacokinetic parameters.
• However, for NANO there was a significant decrease in peak plasma concentration, increase in apparent volume of distribution per fraction absorbed (Vd /F) and increased mean residence time (MRT).

Conclusion

• The one-compartment open model with first-order elimination was found to be the best fit to describe the pharmacokinetics for both groups.
• Neither the ORAL nor NANO forms brought about antinociception, a relief from pain, when administered orally to horses.
• The study concluded that the NANO form did not improve the pharmacokinetics of methadone or lead to an increased systemic body exposure to the drug. This contradicts the general assumption where nanoparticulated drugs are believed to have better drug delivery and systemic exposure.