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

Journal of Veterinary Internal Medicine
K R MuñanaM G Papich

Abstract

Extended-release levetiracetam (LEV-XR) has gained acceptance as an antiepileptic drug in dogs. No studies have evaluated its disposition in dogs with epilepsy. To evaluate the pharmacokinetics of LEV-XR in epileptic dogs when administered alone or with phenobarbital or zonisamide. Eighteen 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). Pharmacokinetic 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. Treatment group accounted for most of the interindividual variation. The LP group had lower CMAX (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 ...Continue Reading

References

Sep 13, 2005·The Veterinary Journal·Kate Chandler
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Jul 29, 2008·Journal of Pharmaceutical Sciences·Marilyn N Martinez, Mark G Papich
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Aug 21, 2015·Journal of Veterinary Internal Medicine·M J Beasley, D M Boothe

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Citations

Jul 14, 2020·Journal of Veterinary Pharmacology and Therapeutics·Kate KuKanichHyun Joo

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