De Graves F J, Riddell M G, Schumacher J
DEpartment of Large Animal Surgery and Medicine, College of Veterinary Medicine, Auburn University, AL 36849-5522, USA.
Am J Vet Res. 1996 Jul;57(7):1031-3.
To determine plasma and milk concentration-time profiles and pharmacokinetic variables after i.v. administration of ketoprofen to lactating dairy cows.
Cows received a single i.v. bolus of ketoprofen (3.31 mg/kg of body weight). Blood and milk were collected at 0, 5, 10, 15, 25, 40, 60, 90, 120, 180, 240, 360, and 480 minutes. Ketoprofen concentrations in plasma and milk were determined.
6-clinically normal lactating Holstein cows.
Plasma and milk samples were processed by solvent extraction, and ketoprofen concentrations were determined, using high-performance liquid chromatography with octadecyl silane reverse-phase guard and analytic columns. A computer polyexponential curve-stripping program was used to fit ketoprofen concentration-time data and to calculate pharmacokinetic variables.
The lower limit of detection for ketoprofen in plasma was 18 ng/ml; the lower limit of quantification was 60 ng/ml. The lower limit of detection for ketoprofen in milk was 27 ng/ml; the lower limit of quantification was 90 ng/ml. Plasma ketoprofen concentration-time curves best fit an open two-compartment pharmacokinetic model. Harmonic mean apparent volume of distribution at steady state was 0.11 (range, 0.095 to 0.13) L/kg, elimination half-life was 0.49 (range, 0.40 to 0.67) hour, and total clearance was 0.17 (range, 0.14 to 0.19) L/kg/h. Ketoprofen was detected in some milk samples, 10 to 120 minutes after administration, but all concentrations were below the limit of quantification. Adverse effects were not observed in cows given ketoprofen.
The elimination of half-life for ketoprofen is short, and low concentrations of ketoprofen can be detected in normal milk, after i.v. treatment of cattle with ketoprofen. Milk and meat from cattle treated i.v. with ketoprofen should not be an important drug residue risk if appropriate withholding periods are used.
测定静脉注射酮洛芬后泌乳奶牛的血浆和乳汁浓度-时间曲线以及药代动力学变量。
奶牛接受单次静脉注射酮洛芬（3.31毫克/千克体重）。在0、5、10、15、25、40、60、90、120、180、240、360和480分钟采集血液和乳汁。测定血浆和乳汁中的酮洛芬浓度。
6头临床正常的泌乳荷斯坦奶牛。
血浆和乳汁样本采用溶剂萃取法处理，使用带有十八烷基硅烷反相保护柱和分析柱的高效液相色谱法测定酮洛芬浓度。使用计算机多指数曲线剥离程序拟合酮洛芬浓度-时间数据并计算药代动力学变量。
血浆中酮洛芬的检测下限为18纳克/毫升；定量下限为60纳克/毫升。乳汁中酮洛芬的检测下限为27纳克/毫升；定量下限为90纳克/毫升。血浆酮洛芬浓度-时间曲线最符合开放二室药代动力学模型。稳态时的调和平均表观分布容积为0.11（范围为0.095至0.13）升/千克，消除半衰期为0.49（范围为0.40至0.67）小时，总清除率为0.17（范围为0.14至0.19）升/千克/小时。给药后10至120分钟在一些乳汁样本中检测到了酮洛芬，但所有浓度均低于定量下限。给奶牛注射酮洛芬后未观察到不良反应。
酮洛芬的消除半衰期较短，静脉注射治疗奶牛后，正常乳汁中可检测到低浓度的酮洛芬。如果使用适当的休药期，静脉注射酮洛芬治疗的奶牛所产的奶和肉不应存在重要的药物残留风险。
