BACKGROUND Enrofloxacin may be an alternative antimicrobial for unresponsive cases of severe bacterial infections in pregnant mares. As pregnancy may affect drug bioavailability, distribution, metabolism and excretion, dose adjustment might be necessary. OBJECTIVES To determine the disposition of orally and intravenously administered enrofloxacin in pregnant and non-pregnant mares. STUDY DESIGN Randomised cross-over experiment. METHODS Six light-breed, healthy pregnant mares (260 days gestation) were given a single dose of either intravenous (5 mg/kg bwt) or oral compounded (7.5 mg/kg bwt) enrofloxacin, with the opposite dose administered after a 7-day washout. The protocol was repeated 45-60 days post-partum, 15-30 days after foals were weaned. Plasma samples were obtained via venepuncture at 0, 5, 10, 20, 30, 45, 60, 90 min, and 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 h after enrofloxacin administration. Enrofloxacin and ciprofloxacin concentrations were measured by LC-MS/MS. Concentration versus time data were analysed based on non-compartmental pharmacokinetics. RESULTS Enrofloxacin AUC0-∞ was significantly higher in pregnant mares than non-pregnant mares after PO administration and tended to be higher after i.v. administration. Ciprofloxacin maximum plasma concentration (Cmax ) and concentration at 24 h (C24h ) were higher, and half-life of the terminal phase (t½λz ) was longer in pregnant mares than non-pregnant mares after oral administration. Similarly, ciprofloxacin C24h was higher in pregnant mares with intravenous administration. Oral bioavailability did not differ based on pregnancy status. MAIN LIMITATIONS Only six healthy light breed mares were assessed. Disease or horse breed may affect the endpoints evaluated. A lack of established enrofloxacin AUC/MIC targets for equine pathogens limits pharmacokinetic-pharmacodynamic conclusions. CONCLUSIONS The oral form of enrofloxacin was well absorbed, and oral bioavailability was comparable to previous studies. While differences in enrofloxacin and ciprofloxacin pharmacokinetics were seen between pregnant and non-pregnant mares, the recommended drug dose and dose intervals are appropriate for MIC <0.25 µg/mL. Dosages may need to be adjusted for bacteria with a MIC >0.25 µg/mL.

中文翻译：

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静脉和口服恩诺沙星对晚期妊娠和未妊娠母马的药代动力学。

背景 恩诺沙星可能是妊娠母马严重细菌感染无反应病例的替代抗微生物剂。由于怀孕可能会影响药物的生物利用度、分布、代谢和排泄，因此可能需要调整剂量。目的 确定妊娠和未妊娠母马口服和静脉注射恩诺沙星的处置情况。研究设计 随机交叉实验。方法 6 只轻种、健康的怀孕母马（妊娠 260 天）给予单剂量静脉注射（5 mg/kg bwt）或口服复方（7.5 mg/kg bwt）恩诺沙星，并在 7-5 天后给予相反剂量。一天冲洗。该方案在产后 45-60 天、马驹断奶后 15-30 天重复。在 0、5、10、20、30、45、60、90 分钟和 2、3、4、6、8 分钟通过静脉穿刺获得血浆样本，恩诺沙星给药后 12、24、36、48 和 72 小时。通过 LC-MS/MS 测量恩诺沙星和环丙沙星的浓度。基于非隔室药代动力学分析浓度对时间的数据。结果 恩诺沙星 AUC0-∞ 在怀孕母马中 PO 给药后显着高于未怀孕母马，并且在 iv 给药后趋于更高。环丙沙星最大血浆浓度（Cmax）和24小时浓度（C24h）较高，妊娠母马口服给药后的终末期半衰期（t½λz）长于非妊娠母马。同样，静脉给药的怀孕母马的环丙沙星 C24h 较高。口服生物利用度没有因妊娠状态而异。主要限制 仅评估了六只健康的轻种母马。疾病或马品种可能会影响评估的终点。缺乏对马病原体确定的恩诺沙星 AUC/MIC 目标限制了药代动力学-药效学结论。结论 口服恩诺沙星吸收良好，口服生物利用度与以往研究相当。虽然在怀孕和未怀孕的母马之间观察到恩诺沙星和环丙沙星的药代动力学差异，但推荐的药物剂量和剂量间隔适用于 MIC <0.25 µg/mL。MIC > 0.25 µg/mL 的细菌可能需要调整剂量。口服生物利用度与以前的研究相当。虽然在怀孕和未怀孕的母马之间观察到恩诺沙星和环丙沙星的药代动力学差异，但推荐的药物剂量和剂量间隔适用于 MIC <0.25 µg/mL。MIC > 0.25 µg/mL 的细菌可能需要调整剂量。口服生物利用度与以前的研究相当。虽然在怀孕和未怀孕的母马之间观察到恩诺沙星和环丙沙星的药代动力学差异，但推荐的药物剂量和剂量间隔适用于 MIC <0.25 µg/mL。MIC > 0.25 µg/mL 的细菌可能需要调整剂量。