摘要
收集临床消化道和呼吸道细菌性疾病猪 2 15头 ,其中原种猪 91头 ,杂交商品猪 12 4头 ;公猪 112头 ,母猪 10 3头 ;体重范围 5～ 4 1kg,平均为 18.6 8± 0 .4 7;日龄 6 3～ 117天 ,平均为 85 .2 4± 0 .78。动物随机分为两组 ,第 1组动物数量为总体数量的 2 / 3,共 14 6头 ,为模型组 ,用于建立群体药动学模型 ;第 2组动物数量为总体动物数量的 1/ 3,共 6 9头 ,为验证组。给药前测定每头猪血清生化指标。试验猪颈部肌肉注射 30 %氟苯尼考注射液 ,剂量为 2 0 mg· kg- 1体重。给药前采一次空白血浆及血清 (测定血清生化指标 ) ,给药后随机采样 ,每只猪采样 2～ 4次 ,就整个群体而言使采样时间均匀分布于药物的吸收相、分布相和消除相内 ,采样时间为给药后 0 .183～ 4 8.36 7h,以高效液相色谱法测定血浆药物浓度 ,应用 NONMEM程序处理所收集的数据 ,包括药时数据、猪只的体重、日龄、性别、种属及血清生化指标、对研究组数据拟合发现最佳药动学模型为一级吸收一室模型 ,药动学参数随机效应及自身变异的最佳模型均为对数加法模型。体重对机体清除率、表观分布容积有显著影响 ,机体清除率、表观分布容积随体重的增加而增加 ,基本呈线性关系。种属对吸收速率常数有显著影响。
sixty-three to one hundred and seventeen days old clinical diseased pigs (112 male,103 female) were used in the study. The body weight of the pigs ranged from 5 kg to 41 kg(18.68±0.47, mean±SE). Among the pigs,91 were purebred pigs and 124 crossbred pigs. 146(2/3 of the total number) were assigned to the study group to develop a population model and 69(1/3 of the total number) were assigned to the validation group to validate the model. Before administration, serum physiological and biochemical parameters for each pig were determined. After intramuscular administraion of the drug at the dose of 20 mg/kg b.w.in the neck muscle,each pig was sampled 2～4 times,with the sampling point evenly distributed in the absorption phase,distribution phase,and elimination phase of the drug. The plasma concentration of florfenicol was measured by a valid HPLC method with UV detector. The pharmacostatistical analysis of the clinical date, including concentration-time data,age,weight,sex,species and serum physiological and biochemical parameters,was conducted with NONMEN software. A one-compartmental model with first absorption best described the data from the study group. Exponential model best described the random effect of the pharmacokinetic parameters and intraindividual variability. Body weight significantly influenced the volume of the central compartment and clearance. Both clearance and volume of the central compartment was linearly correlated to weight Species of the animal had significant effect on the absorption process. When the population pharmacokinetic parameters derived from the study group was applied to validation group, the plot of residuals vs body weight showed homogenous distribution of the residuals,indicating that the pharmacokinetic model,random effect model and population pharmacokinetic parameters obtained from study group were valid. The final population phamacokinetic parameters were obtained from the combined data of study group and validation group. The population typical values for volume of central compartment,clearance,and absorption constant were 7.80 L·kg^(-1), 0.279 L·kg^(-1)·h^(-1), and 2.70 h^(-1) respcetively. The interindividual coefficients of variaibility for volume of central compartment,clearance,and absorption constant were 38.1%, 37.1% and 56.7% respcetively. The residual variability (intraindividual) was 24.9%.
出处
《中国兽医杂志》
CAS
北大核心
2003年第10期32-35,共4页
Chinese Journal of Veterinary Medicine
基金
国家自然科学基金 (3 9970 5 69)
