Plasma disposition of gabapentin after the intragastric administration of escalating doses to adult horses.

Jenifer R Gold,Nicolas F Villarino,Stephen Green,Tamara L Grubb,Sherry Cox

doi:10.1111/jvim.15724

Jenifer R Gold, Nicolas F Villarino + Show 3 more

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https://doi.org/10.1111/jvim.15724

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Abstract

BackgroundIn humans, gabapentin an analgesic, undergoes non‐proportional pharmacokinetics which can alter efficacy. No information exists on the pharmacokinetics of dosages >20 mg/kg, escalating dosages or dose proportionality of gabapentin in horses.Hypothesis and ObjectivesGabapentin exposure in plasma would not increase proportionally relative to the dose in horses receiving dosages ≥20 mg/kg. To assess the plasma pharmacokinetics of gabapentin after nasogastric administration of gabapentin at dosages of 10 to 160 mg/kg in adult horses.AnimalsNine clinically healthy adult Arabian and Quarter Horses.MethodsIn a randomized blinded trial, gabapentin was administered by nasogastric intubation to horses at 10, 20 mg/kg (n = 3) and 60, 80, 120, 160 mg/kg (n = 6). Plasma was collected before and at regular times over 64 hours after administration of gabapentin. Gabapentin was quantified using a validated chromatographic method. Dose proportionality was estimated using a power model. Pharmacokinetic parameters were estimated using compartmental pharmacokinetic analysis.ResultsPlasma pharmacokinetics parameters of gabapentin were estimated after nasogastric administration at dosages of 10 to 160 mg/kg. Gabapentin plasma concentration increased with dose increments. However, the area under the concentration curve from zero to infinity and maximal plasma concentration did not increase proportionally relative to the dose in horses.Conclusions and Clinical ImportanceGabapentin exposure in plasma is not proportional relative to the dose in horses receiving nasogastric dosages of 10 to 160 mg/kg.

Highlights

Laminitis is an extremely painful, debilitating disease of horses, which is devastating to the animals and the animal owners because of the inability to control the pain in horse and the high financial cost/ loss
Our main hypothesis is that doses of gabapentin between 10 and 160 mg/kg administered via nasogastric tube to horses will not increase the plasma concentration in a proportional manner. We addressed this hypothesis by evaluating the plasma pharmacokinetics of gabapentin in horses after a single nasogastric administration at 10, 20, 40, 60, 80, 120, and 160 mg/kg
Plasma pharmacokinetics of gabapentin administered via nasogastric tube to horses at single doses ranging from 10-160 mg/kg are reported here

Summary

| INTRODUCTION

There is a paucity of information on the use of gabapentin in species other than humans, it has been administered to control neuropathic pain in small animals; dosing, and likely the type of disease, complicates gabapentin efficacy in these dogs and cats.[9-16]. Because neuropathic pain can be refractory in many conditions and the extent of pain is highly variable among patients, individualization of treatments and adjustment of dosage regimens are often required for control of individual analgesic needs. It remains to be determined if higher doses of gabapentin result in higher plasma exposure after enteric administration.

| MATERIALS AND METHODS

| RESULTS

Findings

| DISCUSSION