Pharmacokinetics of Single-Dose Oral Pregabalin Administration in Normal Cats

Abstract

Objective: To describe the pharmacokinetic parameters of oral pregabalin in normal cats after single oral dosing.Animals: Six healthy adult research cats.Procedures: Following sedation and indwelling catheter placement, one oral (4 mg/kg) dose of pregabalin was administered. Blood samples were collected at 0, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 h after administration. Plasma pregabalin concentrations were measured by high-performance liquid chromatography and subjected to pharmacokinetic analysis using commercial software.Results: Four of six cats developed moderate sedation after pregabalin administration. The peak pregabalin concentration was 8.3 ± 1.6 μg/ml which occurred at 2.9 ± 1.2 h. Elimination half-life was 10.4 ± 2.6 h and area under the curve was 133.9 ± 71.5 μg-h/ml. Time above the minimum therapeutic concentration for seizure control in dogs and people (2.8 μg/ml) was 17.6 ± 6.2 h. Using these data, predicted minimum, maximum and average steady state concentrations were calculated for 12 and 24 h dosing intervals.Conclusions and Clinical Relevance: Pregabalin (4 mg/kg) administered orally to cats results in plasma concentrations within the range considered to be efficacious for seizure control in dogs and humans between 1.5 and at least 12 h. Because of moderate sedative side effects in the majority of cats at this dose and high calculated maximum steady state concentrations, a lower dose, given more frequently (1–2 mg/kg q 12 h), should be evaluated in prospective clinical studies.

Efficacy of a Single Dose of Pregabalin on Signs of Anxiety in Cats During Transportation—A Pilot Study

“…In that study a dose of 4 mg/kg produced plasma concentrations in the cats that were reported to be similar to those considered efficacious for control of seizures in human patients with epilepsy. However, 4 of the 6 cats in that study showed signs of moderate sedation (26). Sedation is a known side effect in human patients treated with pregabalin (27).…”

“…The most frequently reported adverse event was transient ataxia, which is also reported with gabapentin ( 9 ). Esteban et al ( 26 ) have studied pharmacokinetics of a single dose of pregabalin in oral capsules in healthy cats. In that study a dose of 4 mg/kg produced plasma concentrations in the cats that were reported to be similar to those considered efficacious for control of seizures in human patients with epilepsy.…”

Multimodal analgesia for treatment of allodynia and hyperalgesia after major trauma in a cat

“…53,54 The analgesic response to pregabalin was uncertain in this patient as subanesthetic ketamine CRI was initiated at the same time, and pharmacokinetics in cats indicate that the steady-state concentration is not reached for 2 days. 54…”

“…Its mechanism of action is not related to GABA and is not completely elucidated; however, the compound binds to the alpha2-delta voltage-gated calcium channel subunit, inhibiting calcium influx at the spinal and supraspinal levels and decreasing the release of neurotransmitters, including glutamate and substance P. 53 Pregabalin is used as an anticonvulsant and analgesic in humans, but little information exists for animals, with only one published pharmacokinetic report for cats. 53,54 The analgesic response to pregabalin was uncertain in this patient as subanesthetic ketamine CRI was initiated at the same time, and pharmacokinetics in cats indicate that the steady-state concentration is not reached for 2 days. 54 Tramadol acts in opioidergic, serotoninergic and adrenergic pathways in cats and has elicited thermal antinociception and shown efficacy for treating acute pain in this species.…”

“…53,54 The analgesic response to pregabalin was uncertain in this patient as subanesthetic ketamine CRI was initiated at the same time, and pharmacokinetics in cats indicate that the steady-state concentration is not reached for 2 days. 54 Tramadol acts in opioidergic, serotoninergic and adrenergic pathways in cats and has elicited thermal antinociception and shown efficacy for treating acute pain in this species. [55][56][57] The mu-agonist active metabolite O-desmethyl-tramadol remains high for longer in cats, in comparison with dogs, with a half-life of 261 ± 28 mins (IV administration) and contributes to analgesia.…”