Sams R, Gerken D F, Ashcraft S M
Analytical Toxicology Laboratory, College of Veterinary Medicine, Ohio State University, Columbus 43210, USA.
J Vet Pharmacol Ther. 1995 Apr;18(2):108-16. doi: 10.1111/j.1365-2885.1995.tb00563.x.
The pharmacokinetics and urinary excretion of ketoprofen in six healthy mares after the first and last of five daily intravenous doses of 2.2 mg of ketoprofen per kg body weight were investigated using a high-performance liquid chromatographic (HPLC) method for determining plasma and urinary ketoprofen concentrations. Plasma ketoprofen concentrations declined triexponentially after each dose with no significant differences in plasma concentrations or pharmacokinetic parameter values between the first and last doses. The harmonic mean of the terminal elimination half-life of ketoprofen after the first and last dose was 98.2 and 78.0 min, respectively. The median values of the total plasma clearance and the renal clearance after the first dose were 4.81 and 1.93 mL/min/kg, respectively. Total plasma clearance was attributed to renal excretion of ketoprofen and metabolism of ketoprofen to a base-labile conjugate which was also excreted in the urine. Renal clearance of ketoprofen was attributed to renal tubular secretion since renal clearance was greater than filtration clearance. Urinary recovery of ketoprofen during the first 420 min after the first dose accounted for 26.4% of the dose as unconjugated ketoprofen and 29.8% of the dose as a base-labile conjugate of ketoprofen. Total urinary recovery of ketoprofen as unchanged ketoprofen and from base-labile conjugate represented 56.2% of the dose. Plasma protein binding of ketoprofen was extensive; the mean plasma protein binding of ketoprofen was 92.8% (SD 3.0%) at 500 ng/mL and 91.6% (SD 0.60%) at 10.0 micrograms/mL.
采用高效液相色谱（HPLC）法测定血浆和尿液中酮洛芬浓度，对6匹健康母马每日静脉注射5次、每次每千克体重2.2 mg酮洛芬后，首次和末次给药后酮洛芬的药代动力学和尿排泄情况进行了研究。每次给药后血浆酮洛芬浓度呈三指数下降，首次和末次给药后的血浆浓度或药代动力学参数值无显著差异。首次和末次给药后酮洛芬的终末消除半衰期的调和均值分别为98.2分钟和78.0分钟。首次给药后血浆总清除率和肾清除率的中位数分别为4.81和1.93 mL/（min·kg）。血浆总清除率归因于酮洛芬的肾排泄以及酮洛芬代谢为碱不稳定结合物，该结合物也经尿液排泄。酮洛芬的肾清除率归因于肾小管分泌，因为肾清除率大于滤过清除率。首次给药后前420分钟内，酮洛芬的尿回收率中，未结合酮洛芬占给药剂量的26.4%，酮洛芬碱不稳定结合物占给药剂量的29.8%。以未改变的酮洛芬和碱不稳定结合物形式存在的酮洛芬总尿回收率占给药剂量的56.2%。酮洛芬与血浆蛋白的结合广泛；在500 ng/mL时，酮洛芬的平均血浆蛋白结合率为92.8%（标准差3.0%），在10.0μg/mL时为91.6%（标准差0.60%）。
