Ciribassi John, Luescher Andrew, Pasloske Kirby S, Robertson-Plouch Carol, Zimmerman Alan, Kaloostian-Whittymore Liane
Chicagoland Veterinary Behavior Consultants, 1042 Mountain Glen Way, Carol Stream, IL 60188, USA.
Am J Vet Res. 2003 Aug;64(8):994-8. doi: 10.2460/ajvr.2003.64.994.
To determine bioavailability, pharmacokinetics, and safety for transdermal (TD) and oral administration of fluoxetine hydrochloride to healthy cats.
12 healthy mixed-breed sexually intact 1- to 4-year-old purpose-bred cats.
A single-dose pharmacokinetic study involving 3 groups of 4 cats each was conducted in parallel. Fluoxetine in a formulation of pluronic lecithin organogel (PLO gel) was applied to the hairless portion of the pinnae of cats at 2 dosages (5 or 10 mg/kg), or it was administered orally in capsules at a dosage of 1 mg/kg. Plasma samples were obtained and submitted for liquid chromatography-mass spectrometry-mass spectrometry analysis of fluoxetine and its active metabolite, norfluoxetine.
Peak fluoxetine concentration (Cmax) was lower and time to Cmax longer for TD administration versus oral administration. Relative bioavailability of each dose administered via the TD route was 10% of the value for oral administration of the drug. Mean plasma elimination half-life after oral administration was 47 and 55 hours for fluoxetine and norfluoxetine, respectively.
This study provides evidence that fluoxetine in a 15% (wt:vol) PLO gel formulation can be absorbed through the skin of cats into the systemic circulation. However, the relative bioavailability for TD administration is approximately only 10% of that for the oral route of administration.
确定盐酸氟西汀经皮给药（TD）和口服给药对健康猫的生物利用度、药代动力学及安全性。
12只健康的1至4岁、性成熟的混种目的繁育猫。
进行一项单剂量药代动力学研究，平行设置3组，每组4只猫。将氟西汀制成普朗尼克卵磷脂有机凝胶（PLO凝胶）制剂，以2种剂量（5或10mg/kg）涂于猫耳廓无毛部位，或以1mg/kg的剂量口服胶囊给药。采集血浆样本，进行氟西汀及其活性代谢物去甲氟西汀的液相色谱-质谱-质谱分析。
与口服给药相比，经皮给药时氟西汀的峰值浓度（Cmax）较低，达峰时间较长。经皮给药各剂量的相对生物利用度为口服给药该药物值的10%。口服给药后，氟西汀和去甲氟西汀的平均血浆消除半衰期分别为47小时和55小时。
本研究提供的证据表明，15%（重量/体积）PLO凝胶制剂中的氟西汀可经猫皮肤吸收进入体循环。然而，经皮给药的相对生物利用度约仅为口服给药的10%。
