Brink P, DeGraves F, Ravis W R, Johansen D, Campbell J D, Duran S H
Department of Large Animal Surgery and Medicine, College of Veterinary Medicine, Auburn University, AL 36849-5503, USA.
Am J Vet Res. 1998 Jun;59(6):739-43.
To determine intravascular and intrasynovial pharmacokinetics of the R and S enantiomers of ketoprofen after i.v. and i.m. administration to horses.
6 healthy adult mares.
Horses were weighed and ketoprofen (2.2 mg/kg of body weight) was administered i.v. Blood and synovial fluid samples were obtained and analyzed for concentrations of the R and S enantiomers by means of a modified reverse-phase stereospecific high-pressure liquid chromatographic method. Three weeks later, the procedure was repeated, except that ketoprofen was given IM. Protein binding of ketoprofen enantiomers was determined by means of ultrafiltration. Nonlinear least squares methods were used to calculate pharmacokinetic parameters.
Data obtained after i.v. administration best fit an open, two-compartment model. Mean +/- SD S-to-R serum concentration ratios after i.v. and i.m. administration were 1.36 +/- 0.214 and 1.34 +/- 0.245, respectively. Intrasynovial concentrations of the R and S enantiomers of ketoprofen could be measured for only the first 3 hours after i.v. administration; concentrations were less than the limit of quantification by 4 hours after i.v. administration and at all times after i.m. administration. Extent of protein binding of the R enantiomer was not significantly different from extent of protein binding of the S enantiomer; extent of protein binding did not appear to be concentration dependent. Mean free S-to-free R serum concentration ratios, adjusted for protein binding, after i.v. and i.m. administration were 1.58 and 1.56, respectively.
The R and S enantiomers of ketoprofen are rapidly absorbed and eliminated, have low volumes of distribution, and are highly protein bound.
测定酮洛芬R和S对映体经静脉注射和肌肉注射给予马匹后的血管内和滑膜内药代动力学。
6匹健康成年母马。
对马匹进行称重，静脉注射酮洛芬（2.2 mg/kg体重）。采集血液和滑液样本，采用改良的反相立体特异性高压液相色谱法分析R和S对映体的浓度。3周后重复该过程，不同之处在于酮洛芬采用肌肉注射给药。通过超滤法测定酮洛芬对映体的蛋白结合率。采用非线性最小二乘法计算药代动力学参数。
静脉注射后获得的数据最符合开放二室模型。静脉注射和肌肉注射后，平均±标准差的S与R血清浓度比分别为1.36±0.214和1.34±0.245。酮洛芬R和S对映体的滑膜内浓度仅在静脉注射后的前3小时可测；静脉注射后4小时及肌肉注射后的所有时间，浓度均低于定量限。R对映体的蛋白结合程度与S对映体的蛋白结合程度无显著差异；蛋白结合程度似乎不依赖于浓度。静脉注射和肌肉注射后，经蛋白结合校正的平均游离S与游离R血清浓度比分别为1.58和1.56。
酮洛芬的R和S对映体吸收和消除迅速，分布容积小，且蛋白结合率高。
