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氟苯尼考在大菱鲆(Scophthalmus maximus)中的药代动力学模型:确定药饵中的最佳剂量和给药方式

Pharmacokinetic model of florfenicol in turbot (Scophthalmus maximus): establishment of optimal dosage and administration in medicated feed.

作者信息

de Ocenda V-R, Almeida-Prieto S, Luzardo-Álvarez A, Barja J L, Otero-Espinar F J, Blanco-Méndez J

机构信息

Centro Tecnológico Gallego de Acuicultura (CETGA), CP: 15960, Riveira (A Coruña), Spain.

Departamento de Farmacia y Tecnología Farmacéutica, Universidad de Santiago de Compostela, Santiago de Compostela, Spain.

出版信息

J Fish Dis. 2017 Mar;40(3):411-424. doi: 10.1111/jfd.12525. Epub 2016 Aug 9.

Abstract

The pharmacokinetics of florfenicol (FF) in turbot (Scophthalmus maximus) was studied after single intravenous (10 mg kg ) and oral (100 mg kg ) administration. The plasma concentration-time data of florfenicol were described by an open one-compartment model. The elimination half-life (t ) was estimated to be 21.0 h, and the total body clearance, Cl, was determined as 0.028 L kg h . The apparent volume distribution (V ) was calculated to be 0.86 L kg and the mean residence time (MRT ) was 30.2 h. Following oral administration, the maximum plasma concentration (C ) of 55.4 μg mL was reached at 12 h (T ). The absorption constant (k ) was 0.158 h . The bioavailability was estimated to be 57.1%. The low bioavailability observed at higher doses was explained by the saturation of the mechanisms of absorption. The drug absorption process was limited by its inherent low solubility, which limited the amount of available FF absorbed in the gastrointestinal tract. Based on the pharmacokinetic data, an optimal dosing schedule for FF administration is hereby provided. Based on the minimum inhibitory concentration found for susceptible strains of Aeromonas salmonicida, oral FF administration of first, an initial dose of 30 mg FF kg , followed by 6 maintenance doses at 18 mg kg /daily could be effective against furunculosis in turbot.

摘要

在大菱鲆(Scophthalmus maximus)单次静脉注射(10毫克/千克)和口服(100毫克/千克)氟苯尼考(FF)后,对其药代动力学进行了研究。氟苯尼考的血浆浓度-时间数据用开放的一室模型进行描述。消除半衰期(t)估计为21.0小时,全身清除率Cl确定为0.028升/千克·小时。表观分布容积(V)计算为0.86升/千克,平均驻留时间(MRT)为30.2小时。口服给药后,在12小时(T)达到最大血浆浓度(C)55.4微克/毫升。吸收常数(k)为0.158小时⁻¹。生物利用度估计为57.1%。在较高剂量下观察到的低生物利用度是由吸收机制的饱和所解释的。药物吸收过程受到其固有的低溶解度的限制,这限制了胃肠道中可吸收的氟苯尼考的量。基于药代动力学数据,特此提供氟苯尼考给药的最佳给药方案。根据对杀鲑气单胞菌敏感菌株发现的最低抑菌浓度,口服氟苯尼考,首先初始剂量为30毫克氟苯尼考/千克,随后每天以18毫克/千克进行6次维持剂量给药,可能对大菱鲆的疖疮病有效。

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