土霉素固体脂质纳米粒在家兔体内的药代动力学研究

Pharmacokinetics of oxytetracycline solid lipid nanoparticles in rabbits

【目的】研究土霉素固体脂质纳米粒在家兔体内的药代动力学特征,以评价其应用效果。【方法】将10只家兔随机分为2组,分别按土霉素剂量20mg/kg腹腔注射土霉素固体脂质纳米粒和土霉素注射液,于设定的时间点采血,用HPLC法测定血浆药物质量浓度,并用DAS3.1.0药动学程序计算药代动力学参数。【结果】土霉素注射液与固体脂质纳米粒的达峰质量浓度(Cmax)分别为(3.676±0.376)和(3.699±0.562)mg/L;吸收平衰期(T1/2Ka)分别为(18.570±0.851)和(27.871±1.767)h;0-∞时段药时曲线下的面积(AUC(0-∞))分别为(83.955±3.720)和(170.150±10.403)mg/(L·h);0-∞时段的平均滞留时间(MRT(0-∞))分别为(36.848±0.268)和(44.672±0.392)h。【结论】土霉素制备成固体脂质纳米粒后,具有明显的缓释作用,血药质量浓度达峰值的时间推迟,同时药物在兔体内平均滞留时间明显长于土霉素注射液,生物利用度得以显著提高。

【Objective】This study aimed to evaluate the pharmacokinetics of oxytetracycline solid lipid nanoparticles in rabbits after intraperitoneal injection.【Method】10rabbits were divided into two groups randomly and received single dose of oxytetracycline injection or oxytetracycline solid lipid nanoparticles at20mg/kg by intraperitoneal injection,respectively.The plasma of each rabbit was collected at different times after administration and the plasma concentration of oxytetracycline was determined by HPLC.The pharmacokinetic parameters were analyzed using DAS3.1.0software.【Result】The main pharmacokinetic parameters of oxytetracycline injection and oxytetracycline solid lipid nanoparticles were：Cmax（3.676±0.376）and（3.699±0.562）mg/L,T1/2Ka（18.570±0.851）and（27.871±1.767）h,AUC（0-∞）（83.955±3.720）and（170.150±10.403）mg/（L·h）,and MRT（0-∞）（36.848±0.268）and（44.672±0.392）h,respectively.【Conclusion】Oxytetracycline solid lipid nanoparticles had remarkably sustained release action in rabbits and Tmaxwas significantly delayed.Mean residence time of oxytetracycline solid lipid nanoparticles in rabbit was significantly longer than oxytetracycline injection,and the bioavailability was significantly improved.