Pharmacokinetics and distribution of minocycline in mature horses after oral administration of multiple doses and comparison with minimum inhibitory concentrations

Reasons for performing study: Minocycline holds great potential for use in horses not only for its antimicrobial effects but also for its anti‐inflammatory and neuroprotective properties. However, there are no pharmacokinetic or safety data available regarding the use of oral minocycline in horses. Objectives: To determine pharmacokinetics, safety and penetration into plasma, synovial fluid, aqueous humour (AH) and cerebral spinal fluid (CSF) of minocycline after oral administration of multiple doses in horses and to determine the minimum inhibitory concentrations (MIC) of minocycline for equine pathogenic bacteria. Methods: Six horses received minocycline (4 mg/kg bwt q. 12 h for 5 doses). Thirty‐three blood and 9 synovial fluid samples were collected over 96 h. Aqueous humour and CSF samples were collected 1 h after the final dose. Minocycline concentrations were measured using high pressure liquid chromatography. The MIC values of minocycline for equine bacterial isolates were determined. Results: At steady state, the mean ± s.d. peak concentration of minocycline in the plasma was 0.67 ± 0.26 µg/ml and the mean half‐life was 11.48 ± 3.23 h. The highest trough synovial fluid minocycline concentration was 0.33 ± 0.12 µg/ml. The AH concentration of minocycline was 0.09 ± 0.03 µg/ml in normal eyes and 0.11 ± 0.04 µg/ml in blood aqueous barrier‐disrupted eyes. The mean CSF concentration of minocycline was 0.38 ± 0.09 µg/ml. The MIC values were determined for 301 isolates. Minocycline concentrations were above the MIC₅₀ and MIC₉₀ for many gram‐positive equine pathogens. Potential relevance: This study supports the use of orally administered minocycline at a dose of 4 mg/kg bwt every 12 h for the treatment of nonocular infections caused by susceptible (MIC≤0.25 µg/ml) organisms in horses. Further studies are required to determine the dose that would be effective for the treatment of ocular infections.     

Pharmacokinetics of minocycline in crucian carp (Carassius auratus) after intravenous and oral administration

The pharmacokinetic of minocycline was studied after a single intravenous as well as oral dose (5 mg/kg body weight) in crucian carp (Carassius auratus) reared in freshwater at 10°C. Plasma samples were randomly collected from six fish at each sampling time. Plasma concentrations were determined by high‐performance liquid chromatography and further subjected to noncompartmental analysis. Initial concentration of minocycline just after intravenous administration was calculated as 7.320 μg/ml, while the other parameters after intravenous injection were determined as flows: apparent elimination rate constant (λ_z) of 0.064 per hr, apparent elimination half‐life () of 10.82 hr, total body clearance (Cl) of 142.72 ml/hr/kg, volume of distribution (Vz) of 2,227.38 ml/kg and volume of distribution at steady‐state (Vss) of 1,937.08 ml/kg. While after oral administration, the λ_z, , mean absorption time (MAT), absorption half‐life (t_1/2ka) and bioavailability were determined as 0.059 per hr, 11.74, 5.55, 3.84 hr, and 81.98%, respectively, and the peak concentration was observed as 1.474 ± 0.362 μg/ml at 8 hr. It was shown that minocycline was slowly but relatively completely absorbed, extensively distributed, and slowly eliminated in crucian carp. Based on the ratios of AUC_0–24 hr/MIC90, a minocycline dosage of 5 mg/kg body weight administered intravenously or orally would be only effective to successfully treat crucian carp infected by bacterium with MIC values ≤0.25 μg/ml.     

Minocycline prevents primary duck neurons from duck Tembusu virus-induced death

Duck Tembusu virus (DTMUV), a neurotropic flavivirus, is a causative agent of severe neurological diseases in different birds. No approved vaccines or antiviral therapeutic treatments are available to date. The poultry industry experiences significant economic losses due to DTMUV infections. Minocycline is a second-generation semi-synthetic tetracycline analogue that is commonly used as an antimicrobial treatment. Experimental studies have indicated the successful protective effects of minocycline against neuronal cell death from neurodegenerative diseases and viral encephalitis. The aim of this study was to investigate the effects of minocycline on DTMUV infection in neurons. Primary duck neurons were treated with minocycline, which exhibited neuroprotective effects via anti-apoptotic function rather than through viral replication inhibition. Minocycline might serve as a potential effective drug in DTMUV infection.     

克拉霉素与美满霉素治疗男性非淋菌性尿道炎的疗效比较

目的：观察克拉霉素与美满霉素对男性非淋菌性尿道炎（ＮＧＵ）的疗效及毒副作用。方法：对确诊的７９例ＮＧＵ患者，随机分为克拉霉素组４０例（简称Ａ组）和美满霉素组３９例（简称Ｂ组）。沙眼衣原体（ＣＴ）用ＰＣＲ检测，解脲支原体（ＵＵ）与淋球菌（ＮＧ）用培养检测。结果：Ａ组与Ｂ组的治愈率、总有效率和毒副作用率分别是９５．０％、１００％、１０．０％与６１．５％、８９．７％、５６．４％，两组治愈率及毒副作用率差     

盐酸米诺环素软膏联合甲硝唑缓释药膜治疗慢性牙周炎的疗效观察

目的探讨盐酸米诺环素软膏联合甲硝唑缓释药膜治疗慢性牙周炎的疗效．方法根据治疗方案将138例慢性牙周炎患者分为两组,69例患者使用盐酸米诺环素软膏治疗为对照组,69例患者使用盐酸米诺环素软膏和甲硝唑缓释药膜治疗为观察组,疗程4周,随访1a,比较两组患者的牙周改善情况、治疗效果、不良反应情况、复发情况．结果治疗后,两组患者牙龈指数、菌斑指数、牙齿松动指数、牙周袋深度均显著下降;观察组患者牙龈指数、菌斑指数、牙齿松动指数、牙周袋深度、复发率均明显低于对照组;观察组患者治疗总有效率明显高于对照组,差异均具有统计学意义（P〈0．05）;观察组患者不良反应发生率高于对照组,差异无统计学意义（P〉0．05）．结论盐酸米诺环素软膏联合甲硝唑缓释药膜是治疗慢性牙周炎的有效药物,可明显改善患者的牙周状况,提高药物的治疗效果,不良反应少,且复发率低,值得临床推广使用．     

盐酸米诺环素络合物温敏凝胶的制备及初步评价

【目的】试验旨在制备一种能在局部递送盐酸米诺环素的络合物温敏凝胶。【方法】将盐酸米诺环素与Ca²⁺形成的络合物装载入泊洛沙姆407（P407）与泊洛沙姆188（P188）制备形成的温敏凝胶中，对其温敏性、表征结构、药物含量、稳定性、体外释放效果及抗菌性能进行研究。【结果】本研究制备的盐酸米诺环素温敏凝胶，在其组方为每50 mL凝胶中含米诺环素0.25 g、P407 8 g、P188 1.5 g、CaCl₂ 0.01 g、乙酸调pH至4.0±0.2、其余量为去离子水时，外观性状显示为淡黄色澄清溶液，透明度均匀，无沉淀及药物析出，温敏性能良好（31℃即可发生胶凝）；扫描电镜下可见该凝胶形成的网格孔洞结构致密且分布均匀；平均粒径为11.5 nm，Zeta电位为－3.8 mA；体外释放药物时间长达48 h，与原料药相比明显延长；在抗菌性能检测中，与原料药相比，同浓度盐酸米诺环素络合物温敏凝胶的抑菌能力没有降低，且体外抑菌时间明显延长，抑菌效果良好。【结论】本研究成功制备了一种盐酸米诺环素络合物温敏凝胶，通过模拟体外释放试验及体外抑菌曲线表明该凝胶能显著延长药物作用时间，提高药物利用率，可为临床使用盐酸米诺环素提供一种新的给药方式。