Back to Search
Start Over
Effect of chronic administration of phenobarbital, or bromide, on pharmacokinetics of levetiracetam in dogs with epilepsy.
- Source :
-
Journal of veterinary internal medicine [J Vet Intern Med] 2015 Mar-Apr; Vol. 29 (2), pp. 614-9. Date of Electronic Publication: 2015 Feb 25. - Publication Year :
- 2015
-
Abstract
- Background: Levetiracetam (LEV) is a common add-on antiepileptic drug (AED) in dogs with refractory seizures. Concurrent phenobarbital administration alters the disposition of LEV in healthy dogs.<br />Hypothesis/objectives: To evaluate the pharmacokinetics of LEV in dogs with epilepsy when administered concurrently with conventional AEDs.<br />Animals: Eighteen client-owned dogs on maintenance treatment with LEV and phenobarbital (PB group, n = 6), LEV and bromide (BR group, n = 6) or LEV, phenobarbital and bromide (PB-BR group, n = 6).<br />Methods: Prospective pharmacokinetic study. Blood samples were collected at 0, 1, 2, 4, and 6 hours after LEV administration. Plasma LEV concentrations were determined by high-pressure liquid chromatography. To account for dose differences among dogs, LEV concentrations were normalized to the mean study dose (26.4 mg/kg). Pharmacokinetic analysis was performed on adjusted concentrations, using a noncompartmental method, and area-under-the-curve (AUC) calculated to the last measured time point.<br />Results: Compared to the PB and PB-BR groups, the BR group had significantly higher peak concentration (Cmax ) (73.4 ± 24.0 versus 37.5 ± 13.7 and 26.5 ± 8.96 μg/mL, respectively, P < .001) and AUC (329 ± 114 versus 140 ± 64.7 and 98.7 ± 42.2 h*μg/mL, respectively, P < .001), and significantly lower clearance (CL/F) (71.8 ± 22.1 versus 187 ± 81.9 and 269 ± 127 mL/h/kg, respectively, P = .028).<br />Conclusions and Clinical Importance: Concurrent administration of PB alone or in combination with bromide increases LEV clearance in epileptic dogs compared to concurrent administration of bromide alone. Dosage increases might be indicated when utilizing LEV as add-on treatment with phenobarbital in dogs.<br /> (Copyright © 2015 by the American College of Veterinary Internal Medicine.)
- Subjects :
- Animals
Anticonvulsants administration & dosage
Anticonvulsants pharmacokinetics
Anticonvulsants therapeutic use
Area Under Curve
Bromides administration & dosage
Dog Diseases blood
Dog Diseases metabolism
Dogs
Epilepsy blood
Epilepsy drug therapy
Half-Life
Levetiracetam
Phenobarbital administration & dosage
Piracetam administration & dosage
Piracetam pharmacokinetics
Piracetam therapeutic use
Bromides therapeutic use
Dog Diseases drug therapy
Epilepsy veterinary
Phenobarbital therapeutic use
Piracetam analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1939-1676
- Volume :
- 29
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of veterinary internal medicine
- Publication Type :
- Academic Journal
- Accession number :
- 25711374
- Full Text :
- https://doi.org/10.1111/jvim.12548