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米诺环素在家猫体内的药代动力学。

Pharmacokinetics of minocycline in domestic cats.

作者信息

Tynan Beth E, Papich Mark G, Kerl Marie E, Cohn Leah A

机构信息

Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.

Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.

出版信息

J Feline Med Surg. 2016 Apr;18(4):257-63. doi: 10.1177/1098612X15579114. Epub 2015 Apr 7.

Abstract

OBJECTIVES

Recently, the increased cost and decreased availability of doxycycline has sparked an interest in using minocycline as an alternative. The purpose of this study was to determine the pharmacokinetics of minocycline in domestic cats in order to facilitate dosage decisions.

METHODS

Purpose-bred, young adult cats were administered a single dose of either intravenous (IV; n = 4; 5 mg/kg) or oral (n = 6; 50 mg/cat) minocycline. Blood was collected from each at intervals up to 24 h afterwards. Minocycline was measured using high performance liquid chromatography with ultraviolet detection. A one-compartment pharmacokinetic model was fit to the oral data and a two-compartment model to the IV data via a computer program. Plasma protein binding was measured by fortifying blank plasma from untreated healthy cats with minocycline at two concentrations and applying an ultracentrifugation method.

RESULTS

Two cats became transiently lethargic and tachypneic during IV drug infusion. One cat vomited 6.0 h after infusion, and two cats vomited either 1.5 h or ~5.0 h after oral drug administration. The mean oral dose administered was 13.9 ± 0.47 mg/kg. Oral bioavailability was approximately 62%. Plasma protein binding was 60% at 5 µg/ml and 46% at 1 μg/ml. After IV administration, elimination half-life (t(½)), apparent volume of distribution at steady-state, and systemic clearance were 6.7 h (coefficient of variation [CV] 14.4%), 1.5 l/kg (CV 34.5%) and 2.9 ml/kg/min (CV 40.8%), respectively. After oral administration the terminal t(½) and peak concentration (Cmax) were 6.3 h (CV 9%) and 4.77 µg/ml (CV 36%), respectively.

CONCLUSIONS AND RELEVANCE

Because most bacteria will have a minimum inhibitory concentration of ⩽0.5 μg/ml, an oral dose of 8.8 mg/kg q24h would be adequate to meet pharmacokinetic-pharmacodynamic targets after adjusting for protein binding. Although some gastrointestinal upset may occur, one 50 mg capsule orally q24h would provide appropriate dosing for most cats.

摘要

目的

最近,强力霉素成本增加且可用性降低,引发了使用米诺环素作为替代品的兴趣。本研究的目的是确定米诺环素在家猫体内的药代动力学,以辅助剂量决策。

方法

选用特定培育的年轻成年猫,静脉注射(IV;n = 4;5mg/kg)或口服(n = 6;50mg/只)单剂量米诺环素。此后每隔一段时间采集血样,直至24小时。采用高效液相色谱-紫外检测法测定米诺环素。通过计算机程序对口服数据拟合单室药代动力学模型,对静脉注射数据拟合双室模型。通过用两种浓度的米诺环素强化未治疗健康猫的空白血浆并应用超速离心法来测量血浆蛋白结合率。

结果

两只猫在静脉注射药物期间出现短暂嗜睡和呼吸急促。一只猫在注射后6.0小时呕吐,两只猫在口服药物后1.5小时或约5.0小时呕吐。口服给药的平均剂量为13.9±0.47mg/kg。口服生物利用度约为62%。血浆蛋白结合率在5μg/ml时为60%,在1μg/ml时为46%。静脉注射后,消除半衰期(t(½))、稳态分布容积和全身清除率分别为6.7小时(变异系数[CV]14.4%)、1.5l/kg(CV 34.5%)和2.9ml/kg/min(CV 40.8%)。口服给药后,终末t(½)和峰浓度(Cmax)分别为6.3小时(CV 9%)和4.77μg/ml(CV 36%)。

结论及意义

由于大多数细菌的最低抑菌浓度≤0.5μg/ml,调整蛋白结合率后,口服剂量8.8mg/kg q24h足以达到药代动力学-药效学目标。虽然可能会出现一些胃肠道不适,但每天口服一粒50mg胶囊对大多数猫来说剂量合适。

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