Plasma concentrations of buprenorphine administered via matrix-type transdermal patches applied at three different anatomical locations in healthy adult horses

Abstract

Background: Anatomical location-dependent differences in transdermal opioid penetration are well described in human patients. Although this has been investigated in horses with fentanyl, there is no literature available on location-dependent plasma buprenorphine concentrations when administered as a transdermal matrix-type patch.

Objective: This study aims to compare the plasma concentrations achieved from the matrix-type transdermal buprenorphine patches placed at different anatomical sites (metacarpus, gaskin, and ventral tail base) in healthy adult horses.

Study design: This is a randomized experimental study with a Latin square design.

Methods: Six adult horses were given each of three treatments with a minimum 10-day washout period. For each treatment, two 20 μg h^-1 matrix-type buprenorphine patches were applied to the ventral aspect of the tail base (Tail_TDP), metacarpus region (Metacarpus_TDP), or gaskin region (Gaskin_TDP). Whole blood samples (for determination of buprenorphine concentration) and physiological variables were collected before (0 h) and at 0.5, 2, 4, 6, 8, 10, 12, 16, 24, 32, 48, 56, 72, 96 and 120 h after patches were applied. The patches were removed 96 h following placement and were analyzed for residual buprenorphine content. Buprenorphine concentrations were measured in plasma by LC-MS/MS. A mixed-effects model was used to analyze the physiological variables.

Results: Between the three treatment groups, there was no change in physiological variables across timepoints as compared to baseline and when compared to each other in a single horse and between horses (p > 0.3). When comparing all three locations, the buprenorphine uptake was observed to be more consistent with respect to measurable plasma concentrations >0.1 ng ml^-1 when applied to the ventral aspect of the tail base. In the Tail_TDP group, the mean plasma buprenorphine concentrations were >0.1 ng ml^-1 from 2 to 32 h. The highest group mean was 0.25 ng ml^-1 noted at 4 h.

Conclusions: The metacarpal and gaskin regions presented more erratic and inconsistent buprenorphine uptake and plasma concentrations as compared to the ventral aspect of the tail base. Further research must be directed at investigating the optimal dose, achievable duration of analgesia, change in measurable plasma concentrations, and behavioral and systemic effects.

Keywords: analgesia; equine; gaskin; metacarpus; opioids; pain; pharmacology; tail base.

Figure 1

Placement of two transdermal matrix-type patch systems each containing 20 mg total buprenorphine (20 μg h⁻¹; Amneal Pharmaceuticals LLC., Piscataway, NJ, USA) with dimensions 74 mm × 74 mm and further secured with a 7.62 cm porous elastic adhesive tape covering (Elastikon; Johnson & Johnson, New Brunswick, NJ, USA) on the ventral aspect of the tail base. BUP0 horses did not receive a patch, instead only the elastic adhesive tape was wrapped around the tail base. Hence, the total content was 40 mg, and the dose received was 0.07–0.09 μg kg⁻¹ h⁻¹ based on their body weights on the day of treatment. The three selected patch locations were as follows: (A) Tail_TDP, patch application to the ventral aspect of the tail base; (B) Metacarpus_TDP, patch application to the dorsal surface of the metacarpus; and (C) Gaskin_TDP, patch application to the gaskin region located between stifle and hock joints.

Figure 2

Following instrumentation, baseline data (0 h) was acquired consisting of physical examination and collection of jugular blood samples. Depending on the patch location (ventral aspect of the tail base, metacarpal, and gaskin region), the treatment was initiated by placing two transdermal matrix-type patch systems each containing 20 mg total buprenorphine (20 μg h⁻¹; Amneal Pharmaceuticals LLC., Piscataway, NJ, USA). Hence, the total content was 40 mg, and the dose received was 0.07–0.09 μg kg⁻¹ h⁻¹ based on their body weights on the day of treatment. Following this, 6 ml whole blood samples were obtained for determination of buprenorphine plasma concentration at 0.5, 2, 4, 6, 8, 10, 12, 16, 24, 32, 48, 56, 72, 96, and 120 h after the patches were applied. The transdermal patches were removed at the 96 h timepoint. The last data collection for physiologic variables and blood sampling was performed at 120 h, which marked the end of data collection for that treatment.

Figure 3

Mean ± standard deviation of plasma concentrations of buprenorphine overtime in six horses from baseline (0 h), which coincides with before patch application to 0.5, 2, 4, 6, 8, 10, 12, 16, 24, 32, 48, 56, 72, 96, and 120 h after the patches were applied. Two transdermal matrix-type patch systems each containing 20 mg total buprenorphine (20 μg h⁻¹; Amneal Pharmaceuticals LLC., Piscataway, NJ, USA) were placed in three different locations. Tail, patch application to the ventral aspect of the tail base (orange lines with orange circles); Metacarpus, patch application to the dorsal surface of the metacarpus (blue line with blue circles); and Gaskin, patch application to the gaskin region located between stifle and hock joints (green line with green circles). The total content was 40 mg, and the dose received was 0.07–0.09 μg kg⁻¹ h⁻¹ based on their body weights on the day of treatment. The transdermal patches were removed at the 96 h timepoint.