Goudah A, Shin H C, Shim J H, Abd El-Aty A M
Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
J Vet Pharmacol Ther. 2006 Aug;29(4):307-12. doi: 10.1111/j.1365-2885.2006.00749.x.
The present study was planned to investigate the serum disposition kinetics and the pattern of ceftriaxone elimination in milk and urine of lactating ewes (n = 6) following i.v. and i.m. administration. A crossover study was carried out in two phases separated by 15 days. Ceftriaxone was administered at a dosage of 10 mg/kg b.w. in all animals. Serum, milk and urine samples were collected between 0 and 72 h and a modified agar diffusion bioassay method was used to determine the percentage of protein binding and to measure serum, urine and milk concentrations of ceftriaxone. The drug was detected between 5 min and 48 h postdosing. Concentrations of 0.56 (10 h) and 0.52 (12 h), 0.22 (10 h) and 0.19 (12 h), and 2.18 (24 h) and 2.11 (48 h) mug/mL were measured in serum, milk and urine following i.v. and i.m. administration, respectively. Individual pharmacokinetic parameters were determined by fitting a two-compartment model to the serum and one-compartment open model to the milk concentration-time profiles. After i.v. dosing, the elimination rate constant and elimination half-life were 0.4 +/- 0.05/h and 1.75 +/- 0.02 h, respectively. The volume of distribution at steady state (V(dss)) of 0.28 +/- 0.15 L/kg reflected limited extracellular distribution of the drug with total body clearance (Cl(tot)) of 0.14 +/- 0.10 L/h/kg. Following i.m. administration, the mean T(max obs), C(max obs), t(1/2el) and AUC values for serum data were: 0.75 h, 23.16 +/- 2.94 microg/mL, 1.77 +/- 0.24 h and 67.55 +/- 6.51 microgxh/mL, respectively. For milk the data were: 1.0 h, 8.15 +/- 0.71 mug/mL, 2.2 +/- 0.34 h and 26.6 +/- 5.14 microgxh/mL, respectively. The i.m. bioavailability was 83.6% and the binding percentage of ceftriaxone to serum protein was 33%. Concentrations of ceftriaxone in milk produced by clinically normal mammary glands of ewes were consistently lower than in serum; the kinetic value AUC(milk)/AUC(serum) and C(max milk)/C(max serum) ratios was<0.4. These low values indicated poor distribution and penetration of ceftriaxone from the bloodstream to the mammary gland of lactating ewes following both routes.
本研究旨在探讨静脉注射和肌肉注射后，泌乳母羊（n = 6）血清中的处置动力学以及头孢曲松在乳汁和尿液中的消除模式。采用交叉研究，分两个阶段进行，间隔15天。所有动物均按10 mg/kg体重的剂量给予头孢曲松。在0至72小时内采集血清、乳汁和尿液样本，并采用改良琼脂扩散生物测定法测定蛋白结合百分比，以及测量头孢曲松的血清、尿液和乳汁浓度。给药后5分钟至48小时可检测到该药物。静脉注射和肌肉注射后，血清、乳汁和尿液中的浓度分别为0.56（10小时）和0.52（12小时）、0.22（10小时）和0.19（12小时）、2.18（24小时）和2.11（48小时）μg/mL。通过将二室模型拟合至血清数据以及将一室开放模型拟合至乳汁浓度-时间曲线来确定个体药代动力学参数。静脉给药后，消除速率常数和消除半衰期分别为0.4±0.05/h和1.75±0.02小时。稳态分布容积（V(dss)）为0.28±0.15 L/kg，反映了药物在细胞外的分布有限，总体清除率（Cl(tot)）为0.14±0.10 L/h/kg。肌肉注射后，血清数据的平均T(max obs)、C(max obs)、t(1/2el)和AUC值分别为：0.75小时、23.16±2.94μg/mL、1.77±0.24小时和67.55±6.51μg·h/mL。乳汁的数据分别为：1.0小时、8.
