Alyssa R. Toillion, Michael D. Apley, Johann F. Coetzee, Kushan Kompalage
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引用次数: 0
摘要
对血浆金霉素(CTC)浓度数据进行蒙特卡罗模拟,计算与牛呼吸道疾病病原体 MIC 分布相关的浓度曲线下面积(AUC)值,以评估目标达成率。杂交赫里福德小母牛被随机分配到两个治疗组。治疗组(A)每天按 22 毫克/千克体重的目标剂量连续 5 天服用金霉素(CTC)(n = 8),治疗组(B)每天按 350 毫克/头(根据实际体重计算为 1.5 ± 0.2 毫克/千克)的剂量连续 7 天服用金霉素(CTC)(n = 8)。采用非室分析法计算无血浆药物四氯化碳浓度曲线下的面积。治疗组 A 和 B 的游离药物 AUC 平均观察值(±SD)分别为 4.18 (±1.72) μg × h/mL 和 0.30 (±0.06) μg × h/mL。AUC24/MIC 值为 25 和 12.5 时的达标概率是通过蒙特卡罗模拟计算得出的。当 MIC 值为 0.06 μg/mL 时,治疗组 A 的达标率大于 90%(AUC24/MIC 值为 25),而治疗组 B 在最低 MIC 值(0.015 μg/mL)下的达标率仅为 12.6%(AUC24/MIC 值为 12.5)。考虑到潜在病原体的预期 MIC 分布,两种喂入 CTC 方案都未能获得合理的目标达标率。
Pharmacokinetics and pharmacodynamics of two in-feed chlortetracycline regimens provided to beef cattle
Plasma chlortetracycline (CTC) concentration data were subjected to Monte Carlo simulation of area under the concentration curve (AUC) values related to bovine respiratory disease pathogen MIC distributions to evaluate target attainment rates. Crossbred Hereford heifers were randomly assigned into two treatment groups. Treatment group (A) received chlortetracycline (CTC) at a target dose of 22 mg/kg of bodyweight daily for 5 consecutive days (n = 8) and group (B) received CTC at 350 mg/head per day (1.5 ± 0.2 mg/kg based on actual bodyweights) for seven consecutive days (n = 8). Non-compartmental analysis was used to calculate plasma-free drug CTC area under the concentration curves. The mean observed (±SD) free drug AUC values were 4.18 (±1.72) μg × h/mL and 0.30 (±0.06) μg × h/mL for treatment groups A and B, respectively. The probability of target attainment for AUC24/MIC values of 25 and 12.5 was modeled using Monte Carlo simulations. Treatment group A achieved >90% target attainment (AUC24/MIC of 25) at an MIC of 0.06 μg/mL, whereas treatment group B displayed only 12.6% target attainment (AUC24/MIC of 12.5) at the lowest MIC evaluated (0.015 μg/mL). Both in-feed CTC regimens failed to obtain a reasonable target attainment rate in light of expected MIC distributions of potential pathogens.
期刊介绍:
The Journal of Veterinary Pharmacology and Therapeutics (JVPT) is an international journal devoted to the publication of scientific papers in the basic and clinical aspects of veterinary pharmacology and toxicology, whether the study is in vitro, in vivo, ex vivo or in silico. The Journal is a forum for recent scientific information and developments in the discipline of veterinary pharmacology, including toxicology and therapeutics. Studies that are entirely in vitro will not be considered within the scope of JVPT unless the study has direct relevance to the use of the drug (including toxicants and feed additives) in veterinary species, or that it can be clearly demonstrated that a similar outcome would be expected in vivo. These studies should consider approved or widely used veterinary drugs and/or drugs with broad applicability to veterinary species.