Watts Ashlee E, Nixon Alan J, Papich Mark G, Sparks Holly D, Schwark Wayne S
Comparative Orthopaedics Laboratory, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Vet Surg. 2011 Jul;40(5):563-70. doi: 10.1111/j.1532-950X.2011.00831.x. Epub 2011 May 4.
To determine in vitro elution characteristics of amikacin and ticarcillin from fiber reinforced calcium phosphate beads (FRCP).
Experimental.
FRCP beads with water (A), amikacin (B), ticarcillin/clavulanate (C), or both amikacin and ticarcillin/clavulanate (D) were bathed in mL phosphate-buffered saline (PBS) at 37°C, 5% CO(2) and 95% room air. PBS was sampled (eluent) and beads were placed in fresh PBS at time points 1 and 8 hours and 1, 2, 3, 4, 5, 6, 7, 10, 12, 14, 18, 21, 25, 28, 35, 42, 49, and 56 days. Antibiotic concentration and antimicrobial activity of eluent against Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae were determined.
Both antibiotics eluted in a bimodal pattern. Beads with a single antibiotic eluted 20.8 ± 2.5% of amikacin and 29.5 ± 0.8% of ticarcillin over 56 days. Coelution of the antibiotics resulted in a lower proportion (AUC(0-∞) ) of antibiotics eluted for both amikacin (9.5 ± 0.2%) and ticarcillin (21.7 ± 0.09%). Bioassay of antimicrobial activity of the eluent (t = 1, 8, and 24 hours) established reduced antimicrobial activity of amikacin from combination beads (D).
FRCP beads with amikacin or ticarcillin/clavulanate, but not the combination, are suitable carriers for wound implantation.
Duration before complete resorption of FRCP beads in vivo should be determined before clinical use as a resorbable depot. The results of this study underscore the importance of testing drug combinations, despite success of the combination systemically, before their use in local applications.
测定丁胺卡那霉素和替卡西林从纤维增强磷酸钙珠(FRCP)中的体外洗脱特性。
实验性。
将含有水(A)、丁胺卡那霉素(B)、替卡西林/克拉维酸(C)或丁胺卡那霉素与替卡西林/克拉维酸两者(D)的FRCP珠置于37°C、5%二氧化碳和95%室内空气环境下的毫升磷酸盐缓冲盐水(PBS)中。在第1和8小时以及第1、2、3、4、5、6、7、10、12、14、18、21、25、28、35、42、49和56天对PBS进行采样(洗脱液),并将珠子置于新鲜PBS中。测定洗脱液对大肠杆菌、金黄色葡萄球菌和肺炎克雷伯菌的抗生素浓度及抗菌活性。
两种抗生素均以双峰模式洗脱。含单一抗生素的珠子在56天内洗脱了20.8±2.5%的丁胺卡那霉素和29.5±0.8%的替卡西林。抗生素的共洗脱导致丁胺卡那霉素(9.5±0.2%)和替卡西林(21.7±0.09%)洗脱的抗生素比例(AUC(0-∞))较低。洗脱液抗菌活性的生物测定(时间点为1、8和24小时)显示,联合珠(D)中丁胺卡那霉素的抗菌活性降低。
含丁胺卡那霉素或替卡西林/克拉维酸而非两者联合的FRCP珠是伤口植入的合适载体。
在将FRCP珠作为可吸收贮库临床应用之前,应确定其在体内完全吸收前的持续时间。本研究结果强调了在局部应用中使用药物组合之前进行测试的重要性—尽管该组合在全身应用中取得了成功。