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庆大霉素C1、C2和C2在健康及感染仔猪体内的比较药代动力学

Comparative Pharmacokinetics of Gentamicin C, C and C in Healthy and Infected Piglets.

作者信息

Kim Eun-Young, Kim Tae-Won, Awji Elias Gebru, Lee Eon-Bee, Park Seung-Chun

机构信息

Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, Institute for Veterinary Biomedical Science, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea.

College of Veterinary Medicine and Institute of Veterinary Science, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Republic of Korea.

出版信息

Antibiotics (Basel). 2024 Apr 18;13(4):372. doi: 10.3390/antibiotics13040372.

Abstract

Gentamicin, an aminoglycoside antibiotic, is a mixture of therapeutically active C, C, C and other minor components. Despite its decades-long use in pigs and other species, its intramuscular (IM) pharmacokinetics/pharmacodynamics (PKs/PDs) are unknown in piglets. Furthermore, the PKs of many drugs differ between healthy and sick animals. Therefore, we investigated the PKs of gentamicin after a single IM dose (10 mg/kg) in healthy piglets and piglets that were intranasally co-infected with and (PM). The plasma concentrations were measured using validated liquid chromatography/mass spectrometry. The gentamicin exposure was 36% lower based on the area under the plasma concentration-time curve and 16% lower based on the maximum plasma concentration (C) in the infected piglets compared to the healthy piglets, while it was eliminated faster (shorter half-life and larger clearance) in the infected piglets compared to the healthy piglets. The clearance and volume of distribution were the highest for the C component. C, C and C accounted for 22-25%, 33-37% and 40-42% of the total gentamicin exposure, respectively. The PK/PD target for the efficacy of aminoglycosides (C/minimum inhibitory concentration (MIC) > 10) could be exceeded for PM, with a greater magnitude in the healthy piglets. We suggest integrating this PK information with antibiotic susceptibility data for other bacteria to make informed antibiotic and dosage regimen selections against piglet infections.

摘要

庆大霉素是一种氨基糖苷类抗生素,是具有治疗活性的C、C、C和其他次要成分的混合物。尽管它在猪和其他物种中已使用数十年,但其在仔猪中的肌内(IM)药代动力学/药效学(PKs/PDs)仍不清楚。此外,许多药物的药代动力学在健康动物和患病动物之间存在差异。因此,我们研究了在健康仔猪和经鼻同时感染和(PM)的仔猪中单次肌内注射剂量(10 mg/kg)庆大霉素后的药代动力学。使用经过验证的液相色谱/质谱法测量血浆浓度。与健康仔猪相比,感染仔猪基于血浆浓度-时间曲线下面积的庆大霉素暴露降低了36%,基于最大血浆浓度(C)降低了16%,而与健康仔猪相比,感染仔猪的庆大霉素消除更快(半衰期更短,清除率更大)。C组分的清除率和分布容积最高。C、C和C分别占庆大霉素总暴露量的22-25%、33-37%和40-42%。对于PM,氨基糖苷类药物疗效的PK/PD目标(C/最低抑菌浓度(MIC)>10)可以达到,在健康仔猪中幅度更大。我们建议将这些药代动力学信息与其他细菌的抗生素敏感性数据相结合,以便针对仔猪感染做出明智的抗生素和给药方案选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be68/11047434/14e6c7ea1c41/antibiotics-13-00372-g001.jpg

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