Mileva Rositsa, Rusenov Anton, Milanova Aneliya
Department of Pharmacology, Animal Physiology and Physiological Chemistry, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria.
Department of Internal Noninfectious Diseases, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria.
Antibiotics (Basel). 2021 Mar 17;10(3):310. doi: 10.3390/antibiotics10030310.
Doxycycline is a well-tolerated tetracycline antibiotic, registered for use in rabbits and administered for treatment of bacterial infections in this animal species. Nevertheless, the available pharmacokinetic data are limited and this study aimed to investigate the pharmacokinetics of orally administered doxycycline in mature and immature rabbits by application of the population approach. The rabbits were treated orally with doxycycline hyclate (5 mg/kg bw) in the form of a solid gelatin capsules. Free plasma concentrations were determined with HPLC analysis with Photodiode array detection. The estimated typical value of volume of distribution (tvV), total body clearance, and absorption rate constant were 4.429 L/kg, 1.473 L/kg/h, and 0.257 h, respectively. The highest between-subject variability (BSV) of 69.30% was observed for tvV. Co-variates such as body weight, age, and biochemical parameters did not improve the tested model and did not contribute to explanation of the BSV. The population pharmacokinetic model of the orally administered doxycycline in rabbits should be further developed by addition of data from more animals treated with higher doses. An oral dose of 5 mg/kg could ensure percentage of the time from the dosing interval during which the concentration is above minimum inhibitory concentration (MIC) %fT > MIC of 35% if MIC of 0.18 μg·mL and a dosing interval of 12 h is assumed which does not cover criteria for rational use of antibiotics.
强力霉素是一种耐受性良好的四环素类抗生素，已注册用于兔子，可用于治疗该动物物种的细菌感染。然而，现有的药代动力学数据有限，本研究旨在通过群体方法研究口服强力霉素在成年和未成年兔子体内的药代动力学。给兔子口服盐酸强力霉素（5mg/kg体重），剂型为固体明胶胶囊。采用带光电二极管阵列检测的高效液相色谱分析法测定游离血浆浓度。分布容积（tvV）、全身清除率和吸收速率常数的估计典型值分别为4.429L/kg、1.473L/kg/h和0.257h。tvV的受试者间变异性（BSV）最高，为69.30%。体重、年龄和生化参数等协变量并未改善所测试的模型，也无助于解释BSV。兔子口服强力霉素的群体药代动力学模型应通过增加更多高剂量治疗动物的数据来进一步完善。如果假设最低抑菌浓度（MIC）为0.18μg·mL且给药间隔为12h，口服剂量5mg/kg可确保给药间隔期间浓度高于最低抑菌浓度（%fT>MIC）的时间百分比为35%，但这不符合抗生素合理使用的标准。
