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Pharmacokinetics of single-dose oral pregabalin administration in normal dogs

      Abstract

      Objective

      To describe the pharmacokinetics of pregabalin in normal dogs after a single oral dose.

      Study design

      Prospective experiment.

      Animals

      Six adult Labrador/Greyhound dogs (four females and two males) aged 2.6 (2.6–5.6) years old (median and range) weighing 33.4 (26.8–42.1) kg.

      Methods

      After jugular vein catheterization, the dogs received a single oral dose of pregabalin (∼4 mg kg−1). Blood samples were collected at: 0 (before drug administration), 15 and 30 minutes and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 36 hours after drug administration. Plasma pregabalin concentration was measured by HPLC. Noncompartmental analysis was used to estimate pharmacokinetic variables.

      Results

      No adverse effects were observed. The median (range) pharmacokinetic parameters were: Area under the curve from time 0 to 36 hours = 81.8 (56.5–92.1) μg hour mL−1; absorption half-life = 0.38 (0.25–1.11) hours; elimination half-life = 6.90 (6.21–7.40) hours; time over 2.8 μg mL−1 (the presumed minimal effective concentration) = 11.11 (6.97–14.47) hours; maximal plasma concentration (Cmax) = 7.15 (4.6–7.9) μg mL−1; time for Cmax to occur = 1.5 (1.0–4.0) hours. Assuming an 8-hour dosing interval, predicted minimal, average, and maximal steady state plasma concentrations were 6.5 (4.8–8.1), 8.8 (7.3–10.9), and 13.0 (8.8–15.2) μg mL−1. The corresponding values assuming a 12-hour interval were 3.8 (2.4–4.8), 6.8 (4.9–7.9), and 10.1 (6.6–11.6) μg mL−1.

      Conclusions and clinical relevance

      Pregabalin 4 mg kg−1 PO produces plasma concentrations within the extrapolated therapeutic range from humans for sufficient time to suggest that a twice daily dosing regime would be adequate. Further study of the drug's safety and efficacy for the treatment of neuropathic pain and seizures in dogs is warranted.

      Keywords

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