The pharmacokinetics of single oral dose extended-release topiramate and adverse effects after multi-dose administration in healthy cats

被引:1
作者
Graham, Lindsey T. [1 ]
Foss, Kari D. [1 ]
Reinhart, Jennifer M. [1 ]
Smith, Kathryn M. [1 ,3 ]
Hague, Devon W. [1 ]
Li, Zhong [2 ,4 ]
机构
[1] Univ Illinois, Coll Vet Med, Dept Vet Clin Med, Urbana, IL 61801 USA
[2] Univ Illinois, Metabol Ctr, Roy J Carver Biotechnol Ctr, Urbana, IL USA
[3] Wisconsin Vet Referral Ctr, Waukesha, WI USA
[4] Duke Univ, Sch Med, Ctr Genom & Computat Biol, Duke Prote & Metabol Shared Resource, Durham, NC USA
关键词
antiseizure; epilepsy; feline; glaucoma; seizures; ADJUNCTIVE TREATMENT; USL255; BIOAVAILABILITY;
D O I
10.1111/jvp.13121
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Current treatment options for feline epilepsy are limited to medications that require administration of multiple doses per day or administration of a capsule or large tablet. Expanding the current treatment options could improve patient and owner compliance and optimize seizure control. Topiramate has been used sparingly in veterinary medicine, and limited pharmacokinetic studies have focused on immediate release formulations in dogs. If effective and safe, topiramate extended-release (XR) could broaden the current treatment options for feline epilepsy. The aims of this two-phase study were to establish single-dose pharmacokinetics for topiramate XR in cats, identify a dosing regimen that maintains steady-state plasma drug concentrations within a reference range extrapolated from human medicine (5-20 mu g/mL), and evaluate the safety of topiramate XR in cats following multidose administration. Topiramate XR administered orally at 10 mg/kg once daily for 30 days was sufficient to achieve the desired concentrations in all cats. While no clinically apparent adverse effects were observed, four out of eight cats developed subclinical anemia, calling into question the safety of topiramate XR with chronic administration. Further studies are necessary to better understand the potential adverse effects and overall efficacy of topiramate XR for the treatment of feline epilepsy.
引用
收藏
页码:218 / 228
页数:11
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