猫经口内服2种米尔贝肟吡喹酮片的药代动力学比较研究

本试验将16只成年健康猫随机分成2组,每组8只(公母各半),采用单剂量随机平行对照试验设计,分别单剂量(4 mg/kg体重,以米尔贝肟计)经口内服国产(受试品)和进口(对照品)米尔贝肟吡喹酮片,进行其在猫体内的药代动力学比较研究.给药后按预定时间采集血样,采用HPLC法进行血浆中米尔贝肟和吡喹酮含量的测定,实测血药浓度—时间数据采用Winnonlin 5.2药代动力学分析软件计算药代动力学参数.结果显示,米尔贝肟吡喹酮片对照品单剂量内服后,米尔贝肟的消除半衰期(T_1/2β)为(20.08±7.57)h,达峰时间(T_max)和峰值浓度(C_max)分别为6.00 h和(764.43±251.40)ng/mL,平均曲线下面积(AUC)为(15.00±5.05)ng/(L·h),平均滞留时间(MRT)(18.60±1.52)h;吡喹酮的消除半衰期(T_1/2β)为(6.27±5.26)h,达峰时间(T_max)和峰值浓度(C_max)分别为(3.88±0.35)h和(1018.25±200.19)ng/mL,平均曲线下面积(AUC)为(8.69±2.07)ng/(L·h),平均滞留时间(MRT)(6.56±1.07)h.米尔贝肟吡喹酮片受试品单剂量内服后,米尔贝肟的消除半衰期(T_1/2β)为(15.07±4.05)h,达峰时间(T_max)和峰值浓度(C_max)分别为(5.25±1.04)h和(806.65±299.01)ng/mL,平均曲线下面积(AUC)为(15.18±5.97)ng/(L·h),平均滞留时间(MRT)(17.47±1.97)h,相对生物利用度为101.20%;吡喹酮的消除半衰期(T_1/2β)为(11.11±4.62)h,达峰时间(T_max)和峰值浓度(C_max)分别为(5.25±1.04)h和(880.47±241.27)ng/mL,平均曲线下面积(AUC)为(9.64±2.76)ng/(L·h),平均滞留时间(MRT)(10.52±1.52)h,相对生物利用度为119.16%.与对照品相比,受试品的药代动力学参数中除米尔贝肟的消除半衰期显著缩短、吡喹酮的达峰时间显著延迟外(P<0.05),其他药代动力学参数差异均不显著(P>0.05).结果表明,猫经口内服米尔贝肟吡喹酮片受试品与对照品后具有相似的药代动力学特征.     

Pharmacokinetics and tissue residues of vancomycin after oral administration in crucian carp

The pharmacokinetics and tissue residues of vancomycin in crucian carp (Carassius auratus) were studied after oral administration of a single dosage of 1 mg/kg body weight at water temperature of 18°C. The drug concentration‐time data were fitted using a two‐compartment open model with first‐order absorption. The vancomycin concentrations in plasma and tissues including muscle, liver and kidney were analyzed by means of liquid chromatography‐tandem mass spectrometry. As a result, the plasma absorption rate constant of vancomycin was 3.75/hr and the time point of maximum concentration in plasma was 3.0 hr respectively. The maximum concentration of vancomycin in plasma was 216.58 μg/L. The distribution half‐life and the elimination half‐life in plasma were 6.69 hr and 190 hr, as well as the absorption half‐life of plasma was 0.19/hr. The area under the plasma concentration‐time curve of plasma was 15.12 mg hr/L. The apparent volume of distribution of plasma was estimated to be 4.45 L/kg and the total body clearance was computed as 0.061 L hr^?1 kg^?1. In addition, the maximum tissue concentrations of vancomycin were in the order of liver > kidney > muscle. To guarantee the safety of tissue samples for consumption, it was suggested that the withdrawal time should not be less than 30 days at 18°C. All these results may provide guidance for future vancomycin treatment in aquaculture.     

对乙酰氨基酚琥珀酸酯在家兔体内的药代动力学研究

对乙酰氨基酚琥珀酸酯(AP–S)进入动物机体后能很快分解成对乙酰氨基酚(APAP)。为探明对乙酰氨基酚琥珀酸酯在家兔体内的动力学特征,先建立检测APAP的高效液相色谱法(HPLC),再将6只家兔分别单剂量肌肉注射对乙酰氨基酚琥珀酸酯,采用建立的高效液相色谱法检测家兔体内对乙酰氨基酚的血药浓度;用DAS2.0药代动力学软件计算药代动力学参数。结果显示,给家兔单剂量注射对乙酰氨基酚琥珀酸酯后,主要的药代动力学参数Cmax为(95.44±1.42)mg/L,tmax为0.25 h,AUC(0–∞)为(84.08±7.02)mg/L·h。综合分析表明,对乙酰氨基酚琥珀酸酯在动物体内可迅速转化为对乙酰氨基酚,药物达峰时间短,发挥药效快。