Aktas M, Lefebvre H P, Toutain P L, Braun J P
Département de Physiopathologie & Unité Associée INRA Physiopathologie et Toxicologie Expérimentales, Toulouse, France.
J Vet Pharmacol Ther. 1995 Feb;18(1):1-6. doi: 10.1111/j.1365-2885.1995.tb00542.x.
The fate of skeletal muscle-derived creatine kinase (CK) was investigated in six dogs. After i.m. and i.v. injections of 3000 g and 105,000 g supernatants of dog muscle homogenates, plasma CK activity was measured up to 48 h. There was no significant difference in pharmacokinetic parameters dependent on the type of supernatant injected. After i.v. injection, the volume of distribution of CK was equal to the plasma volume, CK clearance was relatively low (about 0.5 mL/kg/min) and its terminal half-life of elimination was about 2.5 h. After i.m. injection, the CK terminal half-life was about 6.5 h, demonstrating a flip-flop mechanism, i.e. a limiting absorption process from the site of injection. Bioavailability after i.m. injection was about 65%, and the rate of absorption from muscle injection site was relatively slow: peak activity occurred at the second hour post administration, and most CK activity had been absorbed by 24 h. These pharmacokinetic parameters can be used as a basis for a minimally invasive means of quantitating muscle damage either after intramuscular drug administration or in canine sports medicine.
在六只犬中研究了骨骼肌源性肌酸激酶（CK）的转归。经肌肉注射和静脉注射犬肌肉匀浆3000g和105,000g上清液后，测定长达48小时的血浆CK活性。取决于注射上清液的类型，药代动力学参数无显著差异。静脉注射后，CK的分布容积等于血浆容积，CK清除率相对较低（约0.5 mL/kg/min），其终末消除半衰期约为2.5小时。肌肉注射后，CK终末半衰期约为6.5小时，显示出翻转机制，即从注射部位的吸收受限过程。肌肉注射后的生物利用度约为65%，肌肉注射部位的吸收速率相对较慢：给药后第二小时出现峰值活性，到24小时时大部分CK活性已被吸收。这些药代动力学参数可作为在肌肉注射药物后或犬运动医学中定量肌肉损伤的微创方法的基础。
