Pharmacokinetics of single-dose oral pregabalin administration in normal dogs.
OBJECTIVE
To describe the pharmacokinetics of pregabalin in normal dogs after a single oral dose.


METHODS
Prospective experiment.


METHODS
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 ( approximately 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) microg 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 microg mL(-1) (the presumed minimal effective concentration) = 11.11 (6.97-14.47) hours; maximal plasma concentration (C(max)) = 7.15 (4.6-7.9) microg mL(-1); time for C(max) 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) microg 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) microg mL(-1).


CONCLUSIONS
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.
Salazar
Veronica
V
Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Dewey
Curtis W
CW
Schwark
Wayne
W
Badgley
Britton L
BL
Gleed
Robin D
RD
Horne
William
W
Ludders
John W
JW
D000042:Absorption; D000700:Analgesics / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D004285:Dogs / Q000097:blood*; D005260:Female; D006207:Half-Life; D008297:Male; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
D000700:Analgesics; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid