Eichstadt Lauren R, Corriveau Lorraine A, Moore George E, Knipp Gregory T, Cooper Bruce R, Gwin Wilson E
Veterinary Medical Teaching Hospital, University of California-Davis, Davis, California.
Veterinary Teaching Hospital, Purdue University, West Lafayette, Indiana.
Int J Pharm Compd. 2017 May-Jun;21(3):242-246.
The objective of this study was to compare serum concentrations of transdermal fluoxetine compounded in Lipoderm base versus commercially available oral fluoxetine tablets. Sixteen clinically healthy, client-owned cats that were at least one year of age were enrolled. Cats weighed between three and seven kilograms, had no comorbidities, and were behavior medication naïve. Cats were recruited from January 2016 through April 2016. Eight cats were assigned to each medication group based on owner preference. The cats received either oral (1 mg/kg) or transdermal (5 mg/kg; maximum 25 mg daily) fluoxetine compounded in a transdermal base (PCCA Lipoderm), administered daily for 60 days. Serum levels of fluoxetine and norfluoxetine were assessed as a surrogate for relative efficacy. Serum was collected and analyzed by high-performance liquid chromatography-mass spectrometry/mass spectrometry at baseline and days 5, 10, 30, 45, and 60 post-drug start. Adverse effects were monitored during physical exams, speaking with owners, and laboratory analysis of liver function tests at baseline and days 5, 30, and 60 post-drug start. Serum fluoxetine concentrations significantly differed between the treatment groups at days 45 and 60 post-drug start. Norfluoxetine concentrations significantly differed at days 30, 45, and 60 post-drug start. Blood concentrations of fluoxetine and norfluoxetine significantly differed between oral and transdermal routes after 30 days of treatment. Oral fluoxetine concentrations were consistently higher. Transdermal fluoxetine appeared to be well-tolerated, but a lack of knowledge regarding effective blood levels makes it unclear if a clinical effective response would be obtained at the blood concentrations achieved.
本研究的目的是比较复方利多卡因凝胶基质透皮氟西汀与市售口服氟西汀片的血清浓度。招募了16只临床健康、至少一岁的家养猫。猫的体重在3至7千克之间,无合并症,且未曾接受过行为药物治疗。这些猫于2016年1月至2016年4月招募。根据主人的偏好,将8只猫分配到每个药物组。猫接受口服(1毫克/千克)或透皮(5毫克/千克;每日最大剂量25毫克)复方利多卡因凝胶基质透皮氟西汀,每天给药,持续60天。评估氟西汀和去甲氟西汀的血清水平作为相对疗效的替代指标。在基线以及给药开始后第5、10、30、45和60天收集血清,并通过高效液相色谱-质谱/质谱进行分析。在体格检查、与主人交谈以及基线和给药开始后第5、30和60天的肝功能实验室分析期间监测不良反应。给药开始后第45天和60天,治疗组之间的血清氟西汀浓度存在显著差异。给药开始后第30、45和第60天,去甲氟西汀浓度存在显著差异。治疗30天后,口服和透皮途径的氟西汀和去甲氟西汀血药浓度存在显著差异。口服氟西汀浓度始终较高。透皮氟西汀似乎耐受性良好,但由于缺乏关于有效血药浓度的知识,尚不清楚在达到的血药浓度下是否会获得临床有效反应。