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呋塞米在山羊体内静脉注射、肌肉注射和皮下注射的药代动力学。

Pharmacokinetics of furosemide in goats following intravenous, intramuscular, and subcutaneous administrations.

机构信息

Department of Pharmacology, Faculty of Pharmacy, University of Erzincan Binali Yıldırım, Erzincan, Turkey.

Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Kastamonu, Kastamonu, Turkey.

出版信息

J Vet Pharmacol Ther. 2021 Nov;44(6):961-966. doi: 10.1111/jvp.13009. Epub 2021 Aug 24.

Abstract

Furosemide, a loop diuretic drug, is recommended for use in cases of edema, ascites, congestive heart failure, toxicosis, and acute renal failure in goats. However, its pharmacokinetics and bioavailability have not been reported yet in this species. The aim of this study was to determine the pharmacokinetics and bioavailability of furosemide in goats following intravenous (IV), intramuscular (IM), and subcutaneous (SC) administrations at a dose of 2.5 mg/kg. Six clinically healthy goats received furosemide by each route in a three-way crossover pharmacokinetic design with a 15-day washout period between administrations. The plasma concentrations of furosemide were determined using the high-performance liquid chromatography-UV method and analyzed by non-compartmental analysis. The elimination half-life following IV, IM, and SC administration was 0.71 (0.67-0.76) h, 0.69 (0.61-0.74) h, and 0.70 (0.67-0.79) h, respectively. The volume of distribution at steady state and total clearance for the IV route were 0.17 (0.16-0.19) L/kg and 0.30 (0.27-0.33) L/h/kg, respectively. The peak plasma concentrations of furosemide following IM and SC administrations were 11.19 (10.33-11.95) and 6.49 (5.92-7.00) μg/ml at 0.23 (0.16-0.25) and 0.39 (0.33-0.42) h, respectively. The bioavailability was 109.84 (104.92-116.99)% and 70.80 (55.77-86.67)% for the IM and SC routes, respectively. The pharmacokinetics of furosemide following the IV, IM, and SC administrations in goats demonstrated significant differences, which may have clinical and toxicological implications requiring further investigations.

摘要

呋塞米是一种袢利尿剂药物,推荐用于治疗山羊水肿、腹水、充血性心力衰竭、中毒和急性肾衰竭。然而,其药代动力学和生物利用度尚未在该物种中报道。本研究旨在确定静脉(IV)、肌肉内(IM)和皮下(SC)给药 2.5mg/kg 剂量后,呋塞米在山羊中的药代动力学和生物利用度。在三种交叉药代动力学设计中,六只临床健康的山羊通过每种途径接受呋塞米治疗,给药之间有 15 天的洗脱期。使用高效液相色谱-紫外法测定呋塞米的血浆浓度,并采用非房室分析进行分析。IV、IM 和 SC 给药后的消除半衰期分别为 0.71(0.67-0.76)h、0.69(0.61-0.74)h 和 0.70(0.67-0.79)h。IV 途径的稳态分布容积和总清除率分别为 0.17(0.16-0.19)L/kg 和 0.30(0.27-0.33)L/h/kg。IM 和 SC 给药后呋塞米的达峰血浆浓度分别为 11.19(10.33-11.95)μg/ml 和 6.49(5.92-7.00)μg/ml,达峰时间分别为 0.23(0.16-0.25)h 和 0.39(0.33-0.42)h。IM 和 SC 途径的生物利用度分别为 109.84(104.92-116.99)%和 70.80(55.77-86.67)%。在山羊中,IV、IM 和 SC 给药后的呋塞米药代动力学表现出显著差异,这可能具有临床和毒理学意义,需要进一步研究。

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