PDF(Pubmed)
Abstract：
UNASSIGNED: Benzylpenicillin (BP) is a first-line antibiotic in horses but there are discrepancies between manufacturers and literature recommendations regarding dosing regimen. Objectives of this study were to evaluate pharmacokinetics and local tolerance of four different formulations of BP in adult horses, and to suggest optimized dosing regimen according to the formulation.
UNASSIGNED: A cross-over design was used in 3 phases for the intramuscular injection of three different products: procaine BP alone, procaine BP/ benzathine BP combination or penethamate hydriodide were administered IM in the gluteal muscles of 6 horses for 3 days. Single IV administration of sodium BP was performed to the same horses with a dose of 22,000 IU BP/kg bwt 39 weeks after last IM injection. BP plasma concentrations were determined by UPLC assay coupled with mass spectrometry and a PK/PD analysis was conducted to predict the efficacy of various dosing regimens by estimating values of the fT>MIC index for different minimum inhibitory concentrations (MIC). Tolerance at the site of IM injection was monitored by creatine kinase activity quantified with a validated chemistry system and clinical scorings.
UNASSIGNED: Except one neurological reaction following one administration of penethamate hydriodide, the tolerance was good. Procaine BP alone, procaine BP/benzathine BP combination or penethamate hydriodide intramuscular administrations at a dosage of 22,000 IU BP/kg bwt q24h for 5 days would yield plasma concentrations that should be effective against bacteria with MIC of ≤0.256, 0.125 or 0.064 mg/L respectively. Of all the tested treatments, the use of a sodium BP by IV Constant Rate Infusion (CRI) for 10 hours a day was deemed to be the most efficient. All the formulations tested in this study are adequate to treat infections with susceptible Streptococcus equi.
UNASSIGNED: A cross-over design was used in 3 phases for the intramuscular injection of three different products: procaine BP alone, procaine BP/ benzathine BP combination or penethamate hydriodide were administered IM in the gluteal muscles of 6 horses for 3 days. Single IV administration of sodium BP was performed to the same horses with a dose of 22,000 IU BP/kg bwt 39 weeks after last IM injection. BP plasma concentrations were determined by UPLC assay coupled with mass spectrometry and a PK/PD analysis was conducted to predict the efficacy of various dosing regimens by estimating values of the fT>MIC index for different minimum inhibitory concentrations (MIC). Tolerance at the site of IM injection was monitored by creatine kinase activity quantified with a validated chemistry system and clinical scorings.
UNASSIGNED: Except one neurological reaction following one administration of penethamate hydriodide, the tolerance was good. Procaine BP alone, procaine BP/benzathine BP combination or penethamate hydriodide intramuscular administrations at a dosage of 22,000 IU BP/kg bwt q24h for 5 days would yield plasma concentrations that should be effective against bacteria with MIC of ≤0.256, 0.125 or 0.064 mg/L respectively. Of all the tested treatments, the use of a sodium BP by IV Constant Rate Infusion (CRI) for 10 hours a day was deemed to be the most efficient. All the formulations tested in this study are adequate to treat infections with susceptible Streptococcus equi.
摘要：
■苄青霉素（BP）是马的一线抗生素，但制造商和文献推荐的给药方案之间存在差异。本研究的目的是评估四种不同剂型的BP在成年马中的药代动力学和局部耐受性，并根据配方提出优化的给药方案。
■在3个阶段中使用了交叉设计，用于肌内注射三种不同的产品：普鲁卡因BP单药，普鲁卡因BP/苄星BP组合或氢碘化物在6匹马的臀肌中IM给药3天。在最后一次IM注射后39周以22,000IUBP/kgbwt的剂量对相同的马进行BP钠的单次IV施用。通过与质谱联用的UPLC测定确定BP血浆浓度,并进行PK/PD分析以通过估计不同最小抑制浓度(MIC)的fT>MIC指数来预测各种给药方案的功效。通过用经过验证的化学系统和临床评分定量的肌酸激酶活性来监测IM注射部位的耐受性。
■除了一次给予氢碘化物后的一次神经反应，宽容是好的。仅普鲁卡因血压，以22,000IUBP/kgbwtq24h的剂量肌肉内给药普鲁卡因BP/苄星BP组合或氢化苯甲酸盐5天，将产生对MIC≤0.256、0.125或0.064mg/L的细菌有效的血浆浓度。在所有测试的治疗中，通过静脉恒定速率输注(CRI)每天10小时使用钠BP被认为是最有效的。本研究中测试的所有制剂都足以治疗易感的马链球菌感染。
■在3个阶段中使用了交叉设计，用于肌内注射三种不同的产品：普鲁卡因BP单药，普鲁卡因BP/苄星BP组合或氢碘化物在6匹马的臀肌中IM给药3天。在最后一次IM注射后39周以22,000IUBP/kgbwt的剂量对相同的马进行BP钠的单次IV施用。通过与质谱联用的UPLC测定确定BP血浆浓度,并进行PK/PD分析以通过估计不同最小抑制浓度(MIC)的fT>MIC指数来预测各种给药方案的功效。通过用经过验证的化学系统和临床评分定量的肌酸激酶活性来监测IM注射部位的耐受性。
■除了一次给予氢碘化物后的一次神经反应，宽容是好的。仅普鲁卡因血压，以22,000IUBP/kgbwtq24h的剂量肌肉内给药普鲁卡因BP/苄星BP组合或氢化苯甲酸盐5天，将产生对MIC≤0.256、0.125或0.064mg/L的细菌有效的血浆浓度。在所有测试的治疗中，通过静脉恒定速率输注(CRI)每天10小时使用钠BP被认为是最有效的。本研究中测试的所有制剂都足以治疗易感的马链球菌感染。
