The effect of P-glycoprotein on methadone hydrochloride flux in equine intestinal mucosa.

This research study investigates the impact of P-glycoprotein, a transmembrane protein, on the absorption of the analgesic opioid methadone. Findings suggest that P-glycoprotein present in the intestinal mucosa of horses may contribute to the poor intestinal absorption of methadone.

Objective of the study

• The aim of this study is to understand the role of P-glycoprotein in the absorption of methadone, an opioid-based pain relief drug commonly used in equines treatment. Though effective in pain management, the absorption efficacy of methadone has been noted to be lessened due to the presence of P-glycoprotein, particularly found in the intestinal tissues among other locations.

Methodology of the study

• Experimental analysis was conducted using Jejunum tissues (a part of the small intestine) acquired from five horses. These tissues were put into Ussing chambers and were then subjected to methadone solutions, either with or without Rhodamine 123 or verapamil.
• The viability of the tissue samples was assessed using electrical measurements for a duration of 120 minutes. The degree of methadone’s penetration across the jejunal membrane was calculated via measuring the relative drug concentration using an ELISA assay.

Key Findings

• In the comparative analysis, the researchers found that the flux of methadone across the intestinal mucosa was significantly higher only when the methadone solution contained verapamil.
• P-glycoprotein was most abundant in the apical membrane of the jejunal epithelial cells (also known as enterocytes). These proteins were found to be majorly concentrated at the tip of the small, finger-like projections known as villi compared to cells found in the intestinal crypts.
• There is a clear presence of P-glycoprotein in the equine jejunum which is likely to mediate the intestinal transport of methadone.

Conclusions of the study

• This research strongly indicates a role for P-glycoprotein in hampering methadone’s effective intestinal absorption process.
• The findings of this study may pave the way to reconsidering the dosage and delivery methods of methadone in equine treatment. Targeting P-glycoprotein with potential inhibitor substances like verapamil could enhance the bioavailability and efficacy of methadone in horses.