盐酸加替沙星的药代动力学研究

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目的 :研究狗和大鼠口服盐酸加替沙星的吸收、分布和排泄 ,为临床合理用药提供依据。方法 :狗口服盐酸加替沙星 5 ,10和 2 0mg/kg后 0 .2 5 ,0 .5 ,0 .75 ,1,2 ,4,8,12和 2 4h分别从前肢胫前静脉取血 ,用微生物法测定血药浓度并计算药代动力学参数 ;大鼠口服 2 0mg/kg盐酸加替沙星后 5 ,15min和 4h测定各组织的药物浓度 ;对5只大鼠进行胆管插管 ,另 5只置于代谢笼中 ,口服盐酸加替沙星 2 0mg/kg ,48h内分别收集胆汁和尿 ,测定药物累积排除率 ;用透析法测定药物的狗血浆蛋白结合率。结果 :该药药代动力学过程符合一室模型 ,5 ,10和 2 0mg/kg剂量组峰浓度 (Cmax)分别为 2 .0 1,3.18和 8.6 7μg/ml,与血药浓度呈线性关系 ;达峰时间 (Tmax)分别为 1.2 7,1.78和1.6 3h ;吸收半衰期 (t1/2 Ka)分别为 0 .2 8,0 .45和 0 .38h ;消除半衰期 (t1/2 Ke)分别为 5 .78,6 .5 1和 7.36h ;曲线下面积 (AUC)分别为 19.32 ,36 .2 2和 10 5 .45 μg·h/ml。大鼠口服 2 0mg/kg盐酸加替沙星后 ,该药迅速分布于除睾丸、脑以外的各组织中 ,其中肝、肾、胃和肠中分布最多 ,心、肺和脾次之。大鼠口服 2 0mg/kg盐酸加替沙星后 48h ,尿和胆汁累积排泄率分别为 5 3.2 4%和 7.38%。狗血浆蛋白结合率为 (14.45± 1.19) %。结论 :盐酸加? OBJECTIVE: To study the absorption, distribution and excretion of gatifloxacin hydrochloride in dogs and rats and provide basis for clinical rational drug use. METHODS: Dogs received gatifloxacin 5, 10 and 20 mg / kg orally at 2.5, 0.5, 0.75, 1, 2, 4, 8, Blood concentration was measured by microbiological method and the pharmacokinetic parameters were calculated. The drug concentration of each tissue was determined at 5, 15, and 4 hours after oral administration of 20 mg / kg gatifloxacin in rats. The bile duct insertion Tube, and the other 5 were placed in metabolic cages, gatifloxacin hydrochloride 20mg / kg, 48h were collected bile and urine were measured drug cumulative exclusion rate; measured by the dialysis drug dog plasma protein binding rate. RESULTS: The pharmacokinetics of the drug met the one-compartment model. The peak concentrations (Cmax) at 5, 10 and 20 mg / kg were 2.01, 3.18 and 8.67 μg / ml, respectively, which were linear with the plasma concentrations ; Peak time (Tmax) were 1.2 7,1.78 and 1.6 3h respectively; the half-life of absorption (t1 / 2 Ka) were 0.28,0.45 and 0.38 h respectively; the half-life of elimination (t1 / 2 Ke) 5 .78, 5.61 and 7.36 h, respectively. The area under the curve (AUC) was 19.32, 36.22 and 105.545 μg · h / ml, respectively. After oral administration of 20 mg / kg gatifloxacin to rats, the drug rapidly distributed in all tissues except testis and brain, with the most distribution in liver, kidney, stomach and intestine, followed by heart, lung and spleen. After oral administration of 20 mg / kg gatifloxacin 20 h, the cumulative excretion rates of urine and bile were 53.2% and 7.38%, respectively. Dog plasma protein binding rate was (14.45 ± 1.19)%. Conclusion: Hydrochloride plus?
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