CAJ | 학술논문

为了预测喹烯酮在草鱼体内药物残留, 建立其在草鱼体内生理药动学模型.通过搜集大量文献获得鱼的生理解剖参数, 采用已有的喹烯酮试验数据拟合得到药物特异性参数.基于 acslXtreme 生理药动学软件,进行模型假设、血流图设计、质量平衡方程的建立和模型拟合.喹烯酮为小分子药物, 其分布服从血流限速型, 在肝脏代谢, 从肾脏消除.喹烯酮通过口服进入肠道, 然后经肝脏代谢进入血液循环, 因此设定 5 个房室, 即肝、肾、肌肉、肠和其他组织.经过一系列的计算和调试, 最终建立喹烯酮在草体内5室生理药动模型, 成功拟合连续饲喂药物 60d之后的药物残留消除曲线, 其中肝脏中的预测结果比肾脏和肌肉高, 与实测数据一致.因此, 喹烯酮在鱼体内生理药动模型具有一定的应用价值, 将是药物残留检测的新亮点.
위료예측규희동재초어체내약물잔류, 건립기재초어체내생리약동학모형.통과수집대량문헌획득어적생리해부삼수, 채용이유적규희동시험수거의합득도약물특이성삼수.기우 acslXtreme 생리약동학연건,진행모형가설、혈류도설계、질량평형방정적건립화모형의합.규희동위소분자약물, 기분포복종혈류한속형, 재간장대사, 종신장소제.규희동통과구복진입장도, 연후경간장대사진입혈액순배, 인차설정 5 개방실, 즉간、신、기육、장화기타조직.경과일계렬적계산화조시, 최종건립규희동재초체내5실생리약동모형, 성공의합련속사위약물 60d지후적약물잔류소제곡선, 기중간장중적예측결과비신장화기육고, 여실측수거일치.인차, 규희동재어체내생리약동모형구유일정적응용개치, 장시약물잔류검측적신량점.
An effective physiological-based pharmacokinetic (PB-PK) model can be used to analogize and extrapolate the in vivo drug concentrations in different administrations and environments, as well as in different species of animals, hence it has become more and more popular in the drug residual prediction in aquatic animals. In order to predict drug residues of quinocetone in grass carp (Ctenopharyngodon idellus), we established the PB-PK model of quinocetone in this study. We obtained the physiological and anatomical parameters of fish from literatures, and estimated the drug-specific parameters of quinocetone by fitting the existing data. We used the physiological pharmacokinetic soft-ware, asclXtreme, to make the model assumptions, to design the blood flow chart, to generate the mass balance equa-tions and to complete the model fitting. Quinocetone was a small molecule drug, and itsin vivo disposition was blood flow-limited. It was metabolized by the liver and excreted by the kidney. Quinocetone entered the intestine through oral administration and participated in the blood circulation after the metabolism in the liver. Therefore, five rooms were set including the liver, the kidney, the muscles, the intestine and the carcass. We established the 5-room PB-PK model of quinocetone after massive calculation and debugging. We successfully fitted the residual depletion curve after 60 con-secutive days of feeding. The predicted results demonstrated that the drug concentration in the liver was higher than that in the kidney and the muscles, which was consistent with the experimental data. Our PB-PK model of quinocetone in grass carp could be an innovative tool for the test of drug residues.