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美洛昔康在马血浆和尿液中的药代动力学。

Pharmacokinetics of meloxicam in plasma and urine of horses.

作者信息

Toutain Pierre-Louis, Reymond Nadège, Laroute Valérie, Garcia Patrice, Popot Marie-Agnès, Bonnaire Yves, Hirsch Alexandra, Narbe Rüdiger

机构信息

UMR 181 Physiopathologie et Toxicologie Expérimentales, INRA/ENVT, Ecole Nationale Vétérinaire de Toulouse, 23 Chemin des Capelles, 31076 Toulouse, France.

出版信息

Am J Vet Res. 2004 Nov;65(11):1542-7. doi: 10.2460/ajvr.2004.65.1542.

Abstract

OBJECTIVE

To determine pharmacokinetic parameters for meloxicam, a nonsteroidal anti-inflammatory drug, in horses.

ANIMALS

8 healthy horses.

PROCEDURE

In the first phase of the study, horses were administered meloxicam once in accordance with a 2 x 2 crossover design (IV or PO drug administration; horses fed or not fed). The second phase used a multiple-dose regimen (daily oral administration of meloxicam for 14 days), with meloxicam administered at the recommended dosage (0.6 mg/kg). Plasma and urine concentrations of meloxicam were measured by use of validated methods with a limit of quantification of 10 ng/mL for plasma and 20 ng/mL for urine.

RESULTS

Plasma clearance was low (mean +/- SD; 34 +/- 0.5 mL/kg/h), steady-state volume of distribution was limited (0.12 +/- 0.018 L/kg), and terminal half-life was 8.54 +/- 3.02 hours. After oral administration, bioavailability was nearly total regardless of feeding status (98 +/- 12% in fed horses and 85 +/- 19% in nonfed horses). During once-daily administration for 14 days, we did not detect drug accumulation in the plasma. Meloxicam was eliminated via the urine with a urine-to-plasma concentration that ranged from 13 to 18. Concentrations were detected for a relatively short period (3 days) after administration of the final daily dose.

CONCLUSIONS AND CLINICAL RELEVANCE

Results of this study support once-daily administration of meloxicam regardless of the feeding status of a horse and suggest a period of at least 3 days before urine concentrations of meloxicam reach concentrations that could be used in drug control programs.

摘要

目的

测定非甾体抗炎药美洛昔康在马体内的药代动力学参数。

动物

8匹健康马。

过程

在研究的第一阶段,按照2×2交叉设计(静脉注射或口服给药;马进食或未进食)给马单次给予美洛昔康。第二阶段采用多剂量方案(每日口服美洛昔康,持续14天),美洛昔康按推荐剂量(0.6毫克/千克)给药。采用经过验证的方法测定美洛昔康的血浆和尿液浓度,血浆定量限为10纳克/毫升,尿液定量限为20纳克/毫升。

结果

血浆清除率较低(平均值±标准差;34±0.5毫升/千克/小时),稳态分布容积有限(0.12±0.018升/千克),末端半衰期为8.54±3.02小时。口服给药后,无论进食状态如何,生物利用度几乎为100%(进食马中为98±12%,未进食马中为85±19%)。在每日给药14天期间,我们未在血浆中检测到药物蓄积。美洛昔康通过尿液排泄,尿血浆浓度范围为13至18。在最后一次每日给药后,在相对较短的时间段(3天)内检测到了药物浓度。

结论及临床意义

本研究结果支持无论马的进食状态如何,美洛昔康均可每日给药一次,并表明在美洛昔康尿液浓度达到可用于药物控制计划的浓度之前,至少需要3天时间。

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