克拉霉素脂肪乳剂在大鼠体内药动学和组织分布研究

Pharmacokinetics and tissue distribution of clarithromycin emulsion in rats

目的研究克拉霉素脂肪乳剂在大鼠体内药动学和组织中的分布情况,并与克拉霉素注射液相比。方法通过高压均质方法制备克拉霉素脂肪乳剂,通过微生物管碟法测定克拉霉素在大鼠体内血药浓度和组织中药物浓度。结果克拉霉素脂肪乳剂和克拉霉素注射液药-时曲线相似并均符合二室模型,两种剂型的AUC0-t分别为(66.76±16.34)和(59.00±11.20)μg·h/ml。大鼠单剂量静脉注射37.5mg/kg克拉霉素脂肪乳剂和溶液剂后,测定各时间点各组织中药物浓度,以肺为最高。与溶液剂相比,脂肪乳剂提高了脾、肺、肝、肾和脑的药物分布。结论克拉霉素脂肪乳剂与克拉霉素溶液剂血药浓度相似,但脂肪乳剂明显改变了克拉霉素体内组织分布,说明更有助于治疗局部脏器感染。

Objective To determine the drug concentration in plasma and various tissues of rats after intravenous （iv） administration of clarithomycin fat emulsion and clarithromycin aqueous solution using microbiological assay. Method High pressure homogenization method was used to prepare clarithromycin fat emulsion. The levels and distribution of clarithromycin in plasma and tissue after intravenous injection was investigated using cup-plate method. Results The drug concentration-time curve of clarithromycin fat emulsion and clarithromycin aqueous solution are similar and could be described by two compartment model. The parameters of AUC of emulsion and solution were as follows： （66.76± 16.34） μg · h/ml, （59.00 ± 11.20） μg · h/ml. Results showed that the concentration of clarithromycin determined in various tissues and at different time points after iv 37. 5mg/kg fat emulsion and aqueous solution was higher in lung. In vivo distribution showed that fat emulsion increased the uptake of clarithromycin in the tissues of spleen, lung, liver, kidney and brain. Conclusion Fat emulsion significantly changed the in vivo tissue distribution of clafithromycin, which was helpful to increase the therapeutic index of tissue infections.