Pharmacokinetics and pharmacodynamics of repeat dosing of gabapentin in adult horses

Abstract

Background: The repeated administration of high doses of gabapentin may provide better analgesia in horses than current clinical protocols. Hypothesis and Objectives: Administration of gabapentin at 40 and 120 mg/kg PO q 12 h for 14 days will not alter serum biochemistry findings or cause adverse effects. Our objectives were to evaluate the effect of gabapentin on serum biochemistry, physical examination, and plasma pharmacokinetics of gabapentin. Animals: Six healthy adult mares. Methods: Horses received 40 and 120 mg/kg of gabapentin orally q 12 h for 14 days. Horses were examined and scored for ataxia and sedation daily. Serum biochemistry variables were analyzed before treatment and days 7 and 14 after gabapentin administration. Plasma disposition of gabapentin was evaluated after the first and last drug administration. Pharmacokinetic parameters were estimated using noncompartmental analysis. Results: No changes occurred in physiologic or biochemical variables. Median (range) maximal plasma gabapentin concentrations (μg/mL) after the last dose (day 15) were 7.6 (6.2-11) and 22 (14-33) for 40 mg/kg and 120 mg/kg doses respectively. Maximal concentration of gabapentin was reached within 1 hour after drug administration. Repeated administration of gabapentin resulted in a median (range) area under the curve (AUC0-12 hours) last/first dose ratio of 1.5 (1.00-2.63) and 2.92 (1.4-3.8) for the 40 and 120 mg/kg regimens, respectively. Conclusion and Clinical Importance: Our results suggest that horses tolerate gabapentin up to 120 mg/kg PO q 12 h for 14 days. The analgesic effect of the dosage regimens evaluated in our study warrants further research.