Pharmacokinetic profile and behavioral effects of gabapentin in the horse

Abstract

Gabapentin is being used in horses although its pharmacokinetic (PK) profile, pharmacodynamic (PD) effects and safety in the equine are not fully investigated. Therefore, we characterized PKs and cardiovascular and behavioral effects of gabapentin in horses. Gabapentin (20 mg/kg) was administered i.v. or p.o. to six horses using a randomized crossover design. Plasma gabapentin concentrations were measured in samples collected 0-48 h postadministration employing liquid chromatography-tandem mass spectrometry. Blood pressures, ECG, and sedation scores were recorded before and for 12 h after gabapentin dosage. Nineteen quantitative measures of behaviors were evaluated. After i.v. gabapentin, the decline in plasma drug concentration over time was best described by a 3-compartment mammillary model. Terminal elimination half-life (t(1/2γ) ) was 8.5 (7.1-13.3) h. After p.o. gabapentin terminal elimination half-life () was 7.7 (6.7-11.9) h. The mean oral bioavailability of gabapentin (± SD) was 16.2 ± 2.8% indicating relatively poor absorption of gabapentin following oral administration in horses. Gabapentin caused a significant increase in sedation scores for 1 h after i.v. dose only (P < 0.05). Among behaviors, drinking frequency was greater and standing rest duration was lower with i.v. gabapentin (P < 0.05). Horses tolerated both i.v. and p.o. gabapentin doses well. There were no significant differences in and . Oral administration yielded much lower plasma concentrations because of low bioavailability.

Neuropathic Pain Management in Chronic Laminitis

“…In the meantime two studies have been conducted in horses investigating the drug's pharmacokinetic properties as well as behavioral and cardiovascular parameters after IV and PO administration. 126,127 After IV (over 30 min) and PO administration of gabapentin (20 mg/kg), the median elimination half-lives were 8.5 and 7.7 hrs, respectively which correspond well with data in other species. 126 After IV administration plasma gabapentin concentrations remained above the 3-4 µg/mL range for approximately 15 hrs, similar to the dose associated with significant analgesic effects in adult human volunteers.…”

“…Neither route of gabapentin administration was associated with effects on heart rate, rhythm or blood pressure, nor pronounced central nervous effects, which concurs in other species. 127 Further research is required to establish a dosage that will provide effective analgesia in horses with chronic laminitis and to determine if combinations with other agents create an enhanced effect.…”

Analysis of Gabapentin in Equine Plasma with Measurement Uncertainty Estimation by Liquid Chromatography-Tandem Mass Spectrometry

“…The method is capable of providing defensible evidence for identification of GPT in equine plasma. The method has also been successfully used in the analysis of post competition plasma samples obtained from racehorses competing in PA and those collected from research horses post administration of GPT for pharmacokinetic and pharmacodynamic studies (4). The method is fast, sensitive, selective, and reliably reproducible.…”

“…It was approved in 1993 as an antiepileptic drug for use in humans, but recently it is being used as an adjunctive therapy for refractory partial seizures, management of neurotrophic or chronic pain, and early postsurgical pain (2,3). In addition, it is undergoing evaluations in veterinary medicine as an adjunctive therapy in the management of pain in horses with laminitis (4). GPT crosses the blood brain-barrier and this may be the primary site of action.…”

Catastrophic complication following injection and extracorporeal shock wave therapy of a medial femoral condyle subchondral cystic lesion in a 14 year old Arabian mare

“…The analgesic properties of phenylbutazone are well defined (Foreman et al, 2008) and gabapentin was administered to address any neuropathic pain stimulated by the chronicity of the lameness. The oral bioavailability of gabapentin is relatively low and oral doses as high as 20mg/kg have resulted in no apparent adverse side effects in horses (Terry et al, 2010) but the analgesic properties of gabapentin are yet to be clearly established in horses. It is possible that the postoperative analgesic protocol used in this case could have increased the patient's comfort on the affected limb to the point of over-exertion resulting catastrophic failure of the MFC.…”