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加巴喷丁和美洛昔康在荷斯坦-弗里生奶牛中口服联合给药的药代动力学及乳汁分泌情况

Pharmacokinetics and milk secretion of gabapentin and meloxicam co-administered orally in Holstein-Friesian cows.

作者信息

Malreddy P R, Coetzee J F, Kukanich B, Gehring R

机构信息

Department of Clinical Sciences, Kansas State University College of Veterinary Medicine, Manhattan, KS 66506, USA.

出版信息

J Vet Pharmacol Ther. 2013 Feb;36(1):14-20. doi: 10.1111/j.1365-2885.2012.01384.x. Epub 2012 Feb 28.

Abstract

Management of neuropathic pain in dairy cattle could be achieved by combination therapy of gabapentin, a GABA analog and meloxicam, an nonsteroidal anti-inflammatory drug. This study was designed to determine specifically the depletion of these drugs into milk. Six animals received meloxicam at 1 mg/kg and gabapentin at 10 mg/kg, while another group (n=6) received meloxicam at 1 mg/kg and gabapentin at 20 mg/kg. Plasma and milk drug concentrations were determined over 7 days postadministration by HPLC/MS followed by noncompartmental pharmacokinetic analyses. The mean (±SD) plasma C(max) and T(max) for meloxicam (2.89±0.48 μg/mL and 11.33±4.12 h) were not much different from gabapentin at 10 mg/kg (2.87±0.2 μg/mL and 8±0 h). The mean (±SD) milk C(max) for meloxicam (0.41±80.16 μg/mL) was comparable to gabapentin at 10 mg/kg (0.63±0.13 μg/mL and 12±6.69 h). The mean plasma and milk C(max) for gabapentin at 20 mg/kg p.o. were almost double the values at 10 mg/kg. The mean (±SD) milk to plasma ratio for meloxicam (0.14±0.04) was lower than for gabapentin (0.23±0.06). The results of this study suggest that milk from treated cows will have low drug residue concentration soon after plasma drug concentrations have fallen below effective levels.

摘要

奶牛神经性疼痛的管理可通过加巴喷丁(一种GABA类似物)和美洛昔康(一种非甾体抗炎药)的联合治疗来实现。本研究旨在具体确定这些药物在牛奶中的排泄情况。六只动物接受1mg/kg的美洛昔康和10mg/kg的加巴喷丁,而另一组(n = 6)接受1mg/kg的美洛昔康和20mg/kg的加巴喷丁。给药后7天内,通过高效液相色谱/质谱法测定血浆和牛奶中的药物浓度,随后进行非房室药代动力学分析。美洛昔康的平均(±标准差)血浆C(max)和T(max)(2.89±0.48μg/mL和11.33±4.12小时)与10mg/kg的加巴喷丁(2.87±0.2μg/mL和8±0小时)没有太大差异。美洛昔康的平均(±标准差)牛奶C(max)(0.41±80.16μg/mL)与10mg/kg的加巴喷丁(0.63±0.13μg/mL和12±6.69小时)相当。口服20mg/kg加巴喷丁的平均血浆和牛奶C(max)几乎是10mg/kg时的两倍。美洛昔康的平均(±标准差)奶血比(0.14±0.04)低于加巴喷丁(0.23±0.06)。本研究结果表明,在血浆药物浓度降至有效水平以下后不久,经治疗奶牛的牛奶中药物残留浓度将较低。

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