The pharmacokinetics of gabapentin in cats

Abstract

Background: Gabapentin is the most commonly prescribed medication for the treatment of chronic musculoskeletal pain in cats. Despite this common and chronic usage, clinically relevant pharmacokinetic data is lacking.

Objectives: To evaluate the pharmacokinetics of clinically relevant dosing regimens of gabapentin in cats.

Animals: Eight research-purpose mixed-breed cats.

Methods: Cats were enrolled in a serial order, non-randomized pharmacokinetic study. Gabapentin was administered as an IV bolus (5 mg/kg), orally (10 mg/kg) as a single dose or twice daily for 2 weeks, or as a transdermal gel (10 mg/kg) in serial order. Serial blood samples were collected up to 48 hours. Plasma concentrations were determined using Ultra Performance Liquid Chromatography-Mass Spectrometry. Compartmental analysis was used to generate gabapentin time-concentration models.

Results: After IV administration CL (median (range)) and terminal half-life were 160.67 mL/kg*hr (119.63-199.11) and 3.78 hours (3.12-4.47), respectively. The oral terminal half-life was 3.63 hours (2.96-4.77), and 3.72 hours (3.12-4.51) for single and repeated dosing. T_MAX and C_MAX , as predicted by the model were 1.05 hours (0.74-2.11), and 12.42 μg/mL (8.31-18.35) after single oral dosing, and 0.77 hours (0.58-1.64), and 14.78 μg/mL (9.70-18.41) after repeated oral dosing. Bioavailability after a single oral dose was 94.77% (82.46-122.83).

Importance: Repeated oral dosing of gabapentin did not alter the drug's pharmacokinetics, making dose adjustments unnecessary with long-term treatment. As prepared, the transdermal route is an inappropriate choice for drug administration. These relevant data are important for future studies evaluating potential efficacy of the medication for treating chronic pain states in cats.

Keywords: compounded; feline; pain; transdermal.

Figure 1

Gabapentin plasma concentrations after administration as an IV bolus (5 mg/kg) in 8 cats (open diamonds) with modeled time‐concentration curve (using geometric mean of derived parameters; solid line). Samples were collected at 1, 3, 9, 15, 30, and 60 minutes, and then at 2, 4, 6, 8, 12, and 24 hours after IV administration. Data below the limit of quantitation are excluded

Figure 2

Gabapentin plasma concentrations after a single oral dose (10 mg/kg) in 7 cats (closed circles) with modeled time‐concentration curve (using geometric mean of derived parameters; solid line). Samples were collected at 5, 15, 30, 45, 60, and 90 minutes, followed by collection at 2, 4, 8, 12, and 24 hours after oral administration. Data below the limit of quantitation are excluded

Figure 3

Gabapentin plasma concentrations after repeated oral dosing (10 mg/kg) in 7 cats (open circles) with modeled time‐concentration curve (using geometric mean of derived parameters; solid line). Samples were collected at 5, 15, 30, 45, 60, and 90 minutes, followed by collection at 2, 4, 8, 12, 24, and 36 hours after oral administration. Data below the limit of quantitation are excluded

Figure 4

Gabapentin plasma concentrations after single (10 mg/kg; closed circles) and repeated oral dosing (10 mg/kg; open circles) in 7 cats with modeled time‐concentration curve (using geometric mean of derived repeated oral dosing parameters; solid line). Samples were collected at 5, 15, 30, 45, 60, and 90 minutes, followed by collection at 2, 4, 8, 12, and 24 hours after single oral dose administration. After the last repeated oral dose, samples were collected at 5, 15, 30, 45, 60, and 90 minutes, followed by collection at 2, 4, 8, 12, 24, and 36 hours. Data below the limit of quantitation are excluded