Lovasz M, Aarnes T K, Hubbell J A E, Bednarski R M, Lerche P, Lakritz J
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA.
J Vet Pharmacol Ther. 2017 Dec;40(6):663-669. doi: 10.1111/jvp.12403. Epub 2017 Mar 19.
The purpose of the study was to determine pharmacokinetics of fentanyl after intravenous (i.v.) and transdermal (t.d.) administration to six adult alpacas. Fentanyl was administered i.v. (2 μg/kg) or t.d. (nominal dose: 2 μg kg hr ). Plasma concentrations were determined using liquid chromatography-mass spectrometry. Heart rate and respiratory rate were assessed. Extrapolated, zero-time plasma fentanyl concentrations were 6.0 ng/ml (1.7-14.6 ng/ml) after i.v. administration, total plasma clearance was 1.10 L hr kg (0.75-1.40 L hr kg ), volumes of distribution were 0.30 L/kg (0.10-0.99 L/kg), 1.10 L/kg (0.70-2.96 L/kg) and 1.5 L/kg (0.8-3.5 L/kg) for V , V , and V , respectively. Elimination half-life was 1.2 hr (0.5-4.3 hr). Mean residence time (range) after i.v. dosing was 1.30 hr (0.65-4.00 hr). After t.d. fentanyl administration, maximum plasma fentanyl concentration was 1.20 ng/ml (0.72-3.00 ng/ml), which occurred at 25 hr (8-48 hr) after patch placement. The area under the plasma fentanyl concentration-vs-time curve (extrapolated to infinity) after t.d. fentanyl was 61 nghr/ml (49-93 nghr/ml). The dose-normalized bioavailability of fentanyl from t.d. fentanyl in alpacas was 35.5% (27-64%). Fentanyl absorption from the t.d. fentanyl patch into the central compartment occurred at a rate of approximately 50 μg/hr (29-81 μg/hr) between 8 and 72 hr after patch placement.
本研究的目的是确定静脉注射（i.v.）和透皮（t.d.）给予6只成年羊驼后芬太尼的药代动力学。芬太尼通过静脉注射（2μg/kg）或透皮给药（标称剂量：2μg·kg·hr）。使用液相色谱 - 质谱法测定血浆浓度。评估心率和呼吸频率。静脉注射后推算的零时血浆芬太尼浓度为6.0ng/ml（1.7 - 14.6ng/ml），总血浆清除率为1.10L·hr·kg（0.75 - 1.40L·hr·kg），Vdss、Varea和Vss的分布容积分别为0.30L/kg（0.10 - 0.99L/kg）、1.10L/kg（0.70 - 2.96L/kg）和1.5L/kg（0.8 - 3.5L/kg）。消除半衰期为1.2小时（0.5 - 4.3小时）。静脉给药后的平均驻留时间（范围）为1.30小时（0.65 - 4.00小时）。透皮给予芬太尼后，最大血浆芬太尼浓度为1.20ng/ml（0.72 - 3.00ng/ml），在贴片放置后25小时（8 - 48小时）出现。透皮给予芬太尼后血浆芬太尼浓度 - 时间曲线下面积（外推至无穷大）为61ng·hr/ml（49 - 93ng·hr/ml）。羊驼透皮给予芬太尼后芬太尼的剂量归一化生物利用度为35.5%（27 - 64%）。贴片放置后8至72小时之间，芬太尼从透皮贴片中吸收进入中央室的速率约为50μg/hr（29 - 81μg/hr）。
