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速尿对马口服给药后的药代动力学和药效学

Pharmacokinetics and pharmacodynamics of furosemide after oral administration to horses.

作者信息

Johansson Anna M, Gardner Sarah Y, Levine Jay F, Papich Mark G, Lafevers D Heath, Goldman Rebecca B, Sheets M Katie, Atkins Clarke E

机构信息

Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.

出版信息

J Vet Intern Med. 2004 Sep-Oct;18(5):739-43. doi: 10.1892/0891-6640(2004)18<739:papofa>2.0.co;2.

DOI:10.1892/0891-6640(2004)18<739:papofa>2.0.co;2
PMID:15515593
Abstract

Furosemide is the most common diuretic drug used in horses. Furosemide is routinely administered as IV or IM bolus doses 3-4 times a day. Administration PO is often suggested as an alternative, even though documentation of absorption and efficacy in horses is lacking. This study was carried out in a randomized, crossover design and compared 8-hour urine volume among control horses that received placebo, horses that received furosemide at 1 mg/kg PO, and horses that received furosemide at 1 mg/kg IV. Blood samples for analysis of plasma furosemide concentrations, PCV, and total solids were obtained at specific time points from treated horses. Furosemide concentrations were determined by reversed-phase high-performance liquid chromatography with fluorescent detection. Systemic availability of furosemide PO was poor, erratic, and variable among horses. Median systemic bioavailability was 5.4% (25th percentile, 75th percentile: 3.5, 9.6). Horses that received furosemide IV produced 7.4 L (7.1, 7.7) of urine over the 8-hour period. The maximum plasma concentration of 0.03 microg/mL after administration PO was not sufficient to increase urine volume compared with control horses (1.2 L [1.0, 1.4] PO versus 1.2 L [1.0, 1.4] control). There was a mild decrease in urine specific gravity within 1-2 hours after administration of furosemide PO, and urine specific gravity was significantly lower in horses treated with furosemide PO compared with control horses at the 2-hour time point. Systemic availability of furosemide PO was poor and variable. Furosemide at 1 mg/kg PO did not induce diuresis in horses.

摘要

呋塞米是马匹中最常用的利尿药。呋塞米通常以静脉注射或肌肉注射大剂量给药,每天3 - 4次。尽管缺乏马匹口服吸收及疗效的文献记录,但常建议口服给药作为一种替代方法。本研究采用随机交叉设计,比较了接受安慰剂的对照马、口服1 mg/kg呋塞米的马和静脉注射1 mg/kg呋塞米的马在8小时内的尿量。在特定时间点从治疗的马身上采集血样,用于分析血浆呋塞米浓度、红细胞压积和总固体。呋塞米浓度通过反相高效液相色谱荧光检测法测定。口服呋塞米的全身可用性较差,在马匹中不稳定且变化较大。全身生物利用度中位数为5.4%(第25百分位数,第75百分位数:3.5,9.6)。静脉注射呋塞米的马在8小时内产生7.4 L(7.1,7.7)尿液。口服给药后最大血浆浓度为0.03μg/mL,与对照马相比不足以增加尿量(口服1.2 L [1.0,1.4] 对比对照1.2 L [1.0,1.4])。口服呋塞米后1 - 2小时内尿比重略有下降,在2小时时间点,口服呋塞米治疗的马的尿比重显著低于对照马。口服呋塞米的全身可用性较差且变化较大。口服1 mg/kg呋塞米未在马匹中诱导利尿。

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