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Abstract：
BACKGROUND: Pharmacokinetics of amikacin administered IV to neonatal foals are described, but little data are available regarding the plasma concentrations contributed by concurrent intra-articular (IA) administration.
OBJECTIVE: Compare the pharmacokinetics of amikacin when the total dose is administered IV compared to being divided between IV and IA routes of administration in neonatal foals and predict the plasma concentrations from various combined IV and IA dosing regimens.
METHODS: Eight healthy neonatal foals.
METHODS: Foals received 3 amikacin treatment protocols: (1) IV-only (25 mg/kg q24h IV), (2) concurrent IV and IA (16.7 mg/kg q24h IV and 8.3 mg/kg q24h into 1 tarsocrural joint), and (3) IA-only (8.3 mg/kg q24h into 1 tarsocrural joint). Protocols were administered for 3 days beginning at 7, 14, and 21 days of age. Plasma concentrations ≥53 μg/mL at 30 minutes were considered therapeutic for isolates with intermediate susceptibility.
RESULTS: Foal age was a significant variable. The IV-only protocol met or exceeded the 30-minute plasma concentrations considered therapeutic (mean μg/mL [95% confidence interval, CI]) in 7- to 9-day-old (54.0 [52.2-56.9]), 14- to 16-day-old (58.1 [55.2-61.0]), and 21- to 23-day-old (66.6 [63.7-69.6]) foals. Concurrent IV and IA protocol did not reach the 30-minute concentration considered therapeutic in 7- to 9-day-old foals (46.5 [43.6-49.4]) but did in 14- to 16-day-old (62.9 [60.0-65.8]) and 21-to 23-day-old (62.6 [59.7-65.6]) foals.
CONCLUSIONS: Concurrent IV and IA administration of amikacin produces 30-minute plasma concentrations considered therapeutic in foals 14 to 23 days old, but concentrations observed in younger foals might be below those considered therapeutic for isolates with intermediate susceptibility to amikacin.
OBJECTIVE: Compare the pharmacokinetics of amikacin when the total dose is administered IV compared to being divided between IV and IA routes of administration in neonatal foals and predict the plasma concentrations from various combined IV and IA dosing regimens.
METHODS: Eight healthy neonatal foals.
METHODS: Foals received 3 amikacin treatment protocols: (1) IV-only (25 mg/kg q24h IV), (2) concurrent IV and IA (16.7 mg/kg q24h IV and 8.3 mg/kg q24h into 1 tarsocrural joint), and (3) IA-only (8.3 mg/kg q24h into 1 tarsocrural joint). Protocols were administered for 3 days beginning at 7, 14, and 21 days of age. Plasma concentrations ≥53 μg/mL at 30 minutes were considered therapeutic for isolates with intermediate susceptibility.
RESULTS: Foal age was a significant variable. The IV-only protocol met or exceeded the 30-minute plasma concentrations considered therapeutic (mean μg/mL [95% confidence interval, CI]) in 7- to 9-day-old (54.0 [52.2-56.9]), 14- to 16-day-old (58.1 [55.2-61.0]), and 21- to 23-day-old (66.6 [63.7-69.6]) foals. Concurrent IV and IA protocol did not reach the 30-minute concentration considered therapeutic in 7- to 9-day-old foals (46.5 [43.6-49.4]) but did in 14- to 16-day-old (62.9 [60.0-65.8]) and 21-to 23-day-old (62.6 [59.7-65.6]) foals.
CONCLUSIONS: Concurrent IV and IA administration of amikacin produces 30-minute plasma concentrations considered therapeutic in foals 14 to 23 days old, but concentrations observed in younger foals might be below those considered therapeutic for isolates with intermediate susceptibility to amikacin.
摘要：
背景：描述了丁胺卡那霉素对新生马驹的药代动力学，但是关于并发关节内（IA）给药的血浆浓度的数据很少。
目的：比较新生儿马驹静脉注射总剂量时阿米卡星的药代动力学，并预测各种IV和IA联合给药方案的血浆浓度。
方法：8只健康的新生马驹。
方法：Foals接受了3种阿米卡星治疗方案：（1）仅IV（25mg/kgq24hIV），（2）同时IV和IA（16.7mg/kgq24hIV和8.3mg/kgq24h进入1tarsocural关节），和（3）仅IA（8.3mg/kgq24h进入1tar骨关节）。从7、14和21日龄开始给药方案3天。30分钟时的血浆浓度≥53μg/mL被认为是具有中等敏感性的分离株的治疗性。
结果：足龄是一个显著变量。仅IV方案达到或超过30分钟的血浆浓度，被认为是治疗性的（平均μg/mL[95％置信区间，CI])在7天至9天大(54.0[52.2-56.9])，14至16天大（58.1[55.2-61.0]），和21天至23天大（66.6[63.7-69.6]）的小马驹。在7至9天龄的小马驹（46.5[43.6-49.4]）中，同时IV和IA方案未达到30分钟的治疗浓度，但在14至16天龄（62.9[60.0-65.8]）和21至23天龄（62.6[59.7-65.6]）的小马驹中达到了治疗浓度。
结论：阿米卡星的同时IV和IA给药在14至23天龄的小马驹中产生30分钟的血浆浓度，被认为是治疗性的，但是在年轻的小马驹中观察到的浓度可能低于对阿米卡星具有中等敏感性的分离株的治疗浓度。
目的：比较新生儿马驹静脉注射总剂量时阿米卡星的药代动力学，并预测各种IV和IA联合给药方案的血浆浓度。
方法：8只健康的新生马驹。
方法：Foals接受了3种阿米卡星治疗方案：（1）仅IV（25mg/kgq24hIV），（2）同时IV和IA（16.7mg/kgq24hIV和8.3mg/kgq24h进入1tarsocural关节），和（3）仅IA（8.3mg/kgq24h进入1tar骨关节）。从7、14和21日龄开始给药方案3天。30分钟时的血浆浓度≥53μg/mL被认为是具有中等敏感性的分离株的治疗性。
结果：足龄是一个显著变量。仅IV方案达到或超过30分钟的血浆浓度，被认为是治疗性的（平均μg/mL[95％置信区间，CI])在7天至9天大(54.0[52.2-56.9])，14至16天大（58.1[55.2-61.0]），和21天至23天大（66.6[63.7-69.6]）的小马驹。在7至9天龄的小马驹（46.5[43.6-49.4]）中，同时IV和IA方案未达到30分钟的治疗浓度，但在14至16天龄（62.9[60.0-65.8]）和21至23天龄（62.6[59.7-65.6]）的小马驹中达到了治疗浓度。
结论：阿米卡星的同时IV和IA给药在14至23天龄的小马驹中产生30分钟的血浆浓度，被认为是治疗性的，但是在年轻的小马驹中观察到的浓度可能低于对阿米卡星具有中等敏感性的分离株的治疗浓度。
