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

Abstract

Background In 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 Objectives Gabapentin 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. Animals Nine clinically healthy adult Arabian and Quarter Horses. Methods In 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. Results Plasma 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 Importance Gabapentin exposure in plasma is not proportional relative to the dose in horses receiving nasogastric dosages of 10 to 160 mg/kg.

A pilot study of transdermal gabapentin in cats

“…Specific methods and validation of the gabapentin HPLC by the laboratory are described elsewhere. 21 , 22 All experiments were done in triplicate.…”

“…Batched samples were sent for gabapentin concentration analysis to a laboratory utilizing a validated HPLC mass spectrometry method. 21 , 22 …”

“…The limit of quantification for gabapentin at the reference laboratory was 25 ng/mL. Specific methods and validation of the gabapentin HPLC by the laboratory are described elsewhere 21,22 . All experiments were done in triplicate.…”

“…Blood was centrifuged at 2500 rpm for 10 minutes and serum samples immediately frozen at À80 C. Batched samples were sent for gabapentin concentration analysis to a laboratory utilizing a validated HPLC mass spectrometry method. 21,22 2.6 | In vivo phase 2…”

Species Differences in Metabolism of Soluble Epoxide Hydrolase Inhibitor, EC1728, Highlight the Importance of Clinically Relevant Screening Mechanisms in Drug Development

“…Dogs and horses tend to tolerate NSAIDs at higher doses than cats due to limited glucuronyl transferase in cats, but even dogs and horses are not exempt of potential adverse events when using long-term NSAIDs due to gastro-intestinal, kidney and liver toxicities [ 13 , 14 ]. Recently anti-seizure gabapentinoids, such as gabapentin, are being used to treat pain and seizures in companion animals, and despite being a commonly prescribed pain medication for chronic musculoskeletal pain in cats [ 15 ] and highly used in other companion animal species including horses [ 16 ], gabapentin has not been approved for use in companion animals, and assessments are on-going to determine safety and efficacy. Sedation and somnolence are the most frequently described dose-limiting side effects, and withdrawal symptoms, such as rebound pain and agitation which are observed in humans, could further complicate their use in companion animals [ 17 , 18 , 19 ].…”