Pharmacy, College of Medicine and Dentistry, James Cook University, Townsville, Australia.
College of Nursing and Health Sciences, Flinders University, Adelaide, Australia.
BMC Vet Res. 2021 Jan 28;17(1):57. doi: 10.1186/s12917-021-02765-5.
Infectious disease, particularly the fungal disease chytridiomycosis (caused by Batrachochytrium dendrobatidis), is a primary cause of amphibian declines and extinctions worldwide. The transdermal route, although offering a simple option for drug administration in frogs, is complicated by the lack of knowledge regarding percutaneous absorption kinetics. This study builds on our previous studies in frogs, to formulate and predict the percutaneous absorption of a drug for the treatment of infectious disease in frogs. Chloramphenicol, a drug with reported efficacy in the treatment of infectious disease including Batrachochytrium dendrobatidis, was formulated with 20% v/v propylene glycol and applied to the ventral pelvis of Rhinella marina for up to 6 h. Serum samples were taken during and up to 18 h following exposure, quantified for chloramphenicol content, and pharmacokinetic parameters were estimated using non-compartmental analysis.
Serum levels of chloramphenicol reached the minimum inhibitory concentration (MIC; 12.5 μg.mL) for Batrachochytrium dendrobatidis within 90-120 min of exposure commencing, and remained above the MIC for the remaining exposure time. C (17.09 ± 2.81 μg.mL) was reached at 2 h, while elimination was long (t = 18.68 h).
The model, based on in vitro data and adjusted for formulation components and in vivo data, was effective in predicting chloramphenicol flux to ensure the MIC for Batrachochytrium dendrobatidis was reached, with serum levels being well above the MICs for other common bacterial pathogens in frogs. Chloramphenicol's extended elimination means that a 6-h bath may be adequate to maintain serum levels for up to 24 h. We suggest trialling a reduction of the currently-recommended continuous (23 h/day for 21-35 days) chloramphenicol bathing for chytrid infection with this formulation.
传染病，特别是真菌病壶菌病（由蛙壶菌引起），是全球范围内导致两栖动物减少和灭绝的主要原因。尽管经皮途径为青蛙提供了一种简单的药物给药选择，但由于缺乏关于经皮吸收动力学的知识，该途径变得复杂。本研究基于我们之前在青蛙身上的研究，旨在制定和预测用于治疗青蛙传染病的药物的经皮吸收。氯霉素是一种具有治疗传染病（包括蛙壶菌）功效的药物，用 20%（体积/体积）丙二醇配制，并应用于滑蹠蟾的腹侧骨盆，暴露时间长达 6 小时。在暴露期间和暴露后 18 小时内采集血清样本，定量测定氯霉素含量，并使用非房室分析估算药代动力学参数。
血清中氯霉素水平在暴露开始后 90-120 分钟内达到了最低抑菌浓度（MIC；12.5μg·mL），并在剩余的暴露时间内保持在 MIC 以上。在 2 小时时达到 C（17.09±2.81μg·mL），而消除时间较长（t=18.68 小时）。
该模型基于体外数据，并针对配方成分和体内数据进行了调整，可有效预测氯霉素通量，以确保达到蛙壶菌的 MIC，血清水平远高于青蛙中其他常见细菌病原体的 MIC。氯霉素的延长消除意味着 6 小时的浴疗可能足以维持血清水平长达 24 小时。我们建议用这种配方来试验减少目前推荐的连续（23 小时/天，持续 21-35 天）氯毒素浴治疗壶菌感染。
