Pharmacokinetic evaluation of immediate- and extended-release formulations of levetiracetam in dogs

Boozer, Lindsay; Platt, Simon R.; Haley, Allison; Linville, Amie V.; Kent, Marc; Barron, Lauren E.; Nie, Ben; Arnold, Robert D.

doi:10.2460/ajvr.76.8.719

Cited by 12 publications

(16 citation statements)

References 11 publications

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“…The pharmacokinetics of levetiracetam have been extensively evaluated in human patients, dogs, cats, and, more recently, in adult horses [13,14,[22][23][24][25][26]. The results of the current study in foals are similar to those reported in adult horses [14] with minor differences in elimination half-life, volume of distribution and clearance that are likely attributable to agerelated differences in these mechanisms.…”

Section: Discussionsupporting

confidence: 69%

“…Previous studies have evaluated the difference between IR and ER tablets in multiple veterinary species including adult horses. ER formulations of levetiracetam given to adult dogs as an intact tablet were shown to have significantly lower C max , as well as a longer T max as compared with IR formulations [24]. Plasma half-lives and elimination rate constants were not significantly different between preparations.…”

Section: Discussionmentioning

confidence: 87%

“…ER formulations of levetiracetam given to adult dogs as an intact tablet were shown to have significantly lower C max , as well as a longer T max as compared with IR formulations [24]. As extended release (ER) preparations become more prevalent in human medicine, it is possible that immediate release formulations may become less available in the future.…”

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetics of the anticonvulsant levetiracetam in neonatal foals

MacDonald

Hart

Davis

et al. 2017

Equine Veterinary Journal

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetics of the anticonvulsant levetiracetam in neonatal foals

MacDonald

Hart

Davis

et al. 2017

Equine Veterinary Journal

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“…The LP group had lower peak concentration ( C MAX ) and AUC than did the other 2 treatment groups. The values obtained for C MAX and AUC in the L and LZ groups are comparable to those obtained in a previous study evaluating the disposition of LEV‐XR in healthy dogs after single PO dosing at 30 mg/kg …”

Section: Discussionsupporting

confidence: 85%

“…More recently, an extended‐release formulation of levetiracetam (LEV‐XR) became available, and this drug has gained acceptance as an AED in dogs. The pharmacokinetics of LEV‐XR have been evaluated in 2 single dose studies involving healthy dogs, both of which supported q12h dosing to maintain blood concentrations within the reference range for humans (5‐45 μg/mL) . No studies have evaluated the disposition of LEV‐XR when administered as maintenance treatment to dogs with epilepsy, either with or without other AEDs.…”

Section: Introductionmentioning

confidence: 99%

Population pharmacokinetics of extended‐release levetiracetam in epileptic dogs when administered alone, with phenobarbital or zonisamide

Muñana

Otamendi

Nettifee

et al. 2018

Veterinary Internal Medicne

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BackgroundExtended‐release levetiracetam (LEV‐XR) has gained acceptance as an antiepileptic drug in dogs. No studies have evaluated its disposition in dogs with epilepsy.Hypothesis/ObjectivesTo evaluate the pharmacokinetics of LEV‐XR in epileptic dogs when administered alone or with phenobarbital or zonisamide.AnimalsEighteen client‐owned dogs on steady‐state maintenance treatment with LEV‐XR (Group L, n = 6), LEV‐XR and phenobarbital (Group LP, n = 6), or LEV‐XR and zonisamide (Group LZ, n = 6).MethodsPharmacokinetic study. Blood samples were collected at 0, 2, 4, 8, and 12 hours after LEV‐XR was administered with food. Plasma LEV concentrations were determined by high‐pressure liquid chromatography. A population pharmacokinetic approach and nonlinear mixed effects modeling were used to analyze the data.ResultsTreatment group accounted for most of the interindividual variation. The LP group had lower C MAX (13.38 μg/mL) compared to the L group (33.01 μg/mL) and LZ group (34.13 μg/mL), lower AUC (134.86 versus 352.95 and 452.76 hours·μg/mL, respectively), and higher CL/F (0.17 versus 0.08 and 0.07 L/kg/hr, respectively). The half‐life that defined the terminal slope of the plasma concentration versus time curve (~5 hours) was similar to values previously reported for healthy dogs.Conclusions and Clinical ImportanceConsiderable variation exists in the pharmacokinetics of LEV‐XR in dogs with epilepsy being treated with a common dose regimen. Concurrent administration of phenobarbital contributed significantly to the variation. Other factors evaluated, including co‐administration of zonisamide, were not shown to contribute to the variability. Drug monitoring may be beneficial to determine the most appropriate dose of LEV‐XR in individual dogs.

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Pharmacokinetics and Safety of Levetiracetam Extended-Release Tablets and Relative Bioavailability Compared with Immediate-Release Tablets in Healthy Chinese Subjects

Wang

Quan-ying

et al. 2018

Eur J Drug Metab Pharmacokinet

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After single and multiple doses, the absorption of levetiracetam ER was equal to IR, the t was significantly delayed, and the C and C were significantly decreased. Food did not affect the absorption of the levetiracetam ER tablet, but the C increased and the t was delayed. The levetiracetam ER tablet was well tolerated and found to be dose proportional from 500 to 2000 mg in healthy Chinese subjects.

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Pharmacokinetic evaluation of immediate- and extended-release formulations of levetiracetam in dogs

Cited by 12 publications

References 11 publications

Pharmacokinetics of the anticonvulsant levetiracetam in neonatal foals

Pharmacokinetics of the anticonvulsant levetiracetam in neonatal foals

Population pharmacokinetics of extended‐release levetiracetam in epileptic dogs when administered alone, with phenobarbital or zonisamide

Pharmacokinetics and Safety of Levetiracetam Extended-Release Tablets and Relative Bioavailability Compared with Immediate-Release Tablets in Healthy Chinese Subjects

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