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替米考星在鹅单次和多次口服给药后的药代动力学及抗菌活性

Pharmacokinetics and antibacterial activity of tiamulin after single and multiple oral administrations in geese.

作者信息

Sartini Irene, Vercelli Cristina, Lebkowska-Wieruszewska Beata, Lisowski Andrzej, Fadel Charbel, Poapolathep Amnart, Dessì Filomena, Giorgi Mario

机构信息

Department of Veterinary Medicine, University of Sassari, Sassari, Italy.

Department of Veterinary Sciences, University of Turin, Torino, Italy.

出版信息

Vet Anim Sci. 2023 Oct 21;22:100317. doi: 10.1016/j.vas.2023.100317. eCollection 2023 Dec.

Abstract

Tiamulin is an antibiotic approved exclusively in veterinary medicine, active against G-positive bacteria as well as Mycoplasma spp. and Leptospirae spp. The study was aimed to establish its pharmacokinetics and to evaluate drug effects on resistance in cloacal flora in geese. Eight healthy geese underwent to a two-phase longitudinal study (60 mg/kg single oral administration 60 mg/kg/day for 4 days) with a two-week wash-out period. Blood samples and cloacal swabs were collected at pre-assigned times. Minimal inhibitory concentration (MIC) has been evaluated for each isolated bacterial species. The pharmacokinetic parameters that significantly differed between the groups were C ( = 0.024), AUC ( = 0.031), AUC ( = 0.038), t1/2 ( = 0.021), Cl/F ( = 0.036), and Vd/F ( = 0.012). Tiamulin exhibited a slow to moderate terminal half-life (3.13 h single; 2.62 h multiple) and a rapid absorption (1 h single; 0.5 h multiple) in geese, with an accumulation ratio of 1.8 after multiple doses. An simulation of multiple dosing did not reflect the results of the multiple dosage study. In both treatments, the MIC values were very high demonstrating a resistance (> 64 μg/ml) against tiamulin that can be present prior the drug administration for some strains, or emerge shortly after the commencing of treatment for some others.

摘要

替米考星是一种仅被批准用于兽医学的抗生素,对革兰氏阳性菌、支原体属和钩端螺旋体属有活性。该研究旨在确定其药代动力学,并评估药物对鹅泄殖腔菌群耐药性的影响。八只健康鹅进行了一项两阶段的纵向研究(单次口服给药60毫克/千克,连续4天每天60毫克/千克),洗脱期为两周。在预先设定的时间采集血样和泄殖腔拭子。对每种分离出的细菌物种评估了最低抑菌浓度(MIC)。两组之间有显著差异的药代动力学参数为C(P = 0.024)、AUC(P = 0.031)、AUC(P = 0.038)、t1/2(P = 0.021)、Cl/F(P = 0.036)和Vd/F(P = 0.012)。替米考星在鹅体内表现出缓慢至中等的末端半衰期(单次给药3.13小时;多次给药2.62小时)和快速吸收(单次给药1小时;多次给药0.5小时),多次给药后的蓄积比为1.8。多次给药模拟未反映多次给药研究的结果。在两种治疗中,MIC值都非常高,表明对替米考星存在耐药性(> 64微克/毫升),对于某些菌株,这种耐药性可能在给药前就已存在,而对于其他一些菌株,则可能在治疗开始后不久出现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65c5/10618762/b409b51a918c/gr1.jpg

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