Toutain P L, Lassourd V, Costes G, Alvinerie M, Bret L, Lefebvre H P, Braun J P
Ecole Nationale Vétérinaire de Toulouse, Département de Physiopathologie, France.
J Vet Pharmacol Ther. 1995 Jun;18(3):226-35. doi: 10.1111/j.1365-2885.1995.tb00583.x.
The present study was undertaken to measure the weight of muscle destroyed by an intramuscular injection of phenylbutazone (PBZ) in horses. In six horses, CK disposition parameters were evaluated after intravenous (i.v.) and intramuscular (i.m.) administration of a CK horse preparation. The same horses received PBZ, a potentially irritating agent, by i.v. and i.m. (neck and hindquarter) routes. Data were analysed using compartmental approaches and instantaneous CK flux was calculated using a discrete deconvolution method. For a 150 U/kg CK dose, the steady-state volume of distribution was 0.050 +/- 0.0115 L/kg and the plasma half-life was 112 +/- 18 min. After CK i.m. administration, the half-life of the terminal phase was 11.8 +/- 5.3 h indicating a flip-flop process and the mean bioavailability of CK was close to 100%. After PBZ i.m. administration, the CK activity was significantly increased with peak values of 508 +/- 109 U/L after the neck administration and 873 +/- 365 U/L after the gluteal administration. By measuring the total amount of CK released from injured muscle, it was calculated that an equivalent of 0.044 +/- 0.029 g/kg of muscle was destroyed after PBZ administration in the neck. The corresponding figure was 0.118 +/- 0.048 g/kg after intragluteal PBZ administration. By deconvoluting plasma CK activity, it was shown that the CK entry rate was maximum for the first 30-60 min following PBZ administration, which then decreased slowly to return to the control value after a delay of 24-48 h after PBZ administration. It was concluded that the CK release pattern following a controlled muscular damage was a non-invasive approach useful for quantifying the amount of damaged muscle, and that the calculation of CK input rate by deconvolution was of potential interest in describing events at the muscle cell level.
本研究旨在测定马肌肉内注射保泰松（PBZ）后被破坏的肌肉重量。对6匹马静脉注射（i.v.）和肌肉注射（i.m.）CK马制剂后评估CK处置参数。相同的马匹通过静脉注射和肌肉注射（颈部和后躯）途径接受PBZ（一种潜在刺激性药物）。使用房室模型方法分析数据，并使用离散反卷积方法计算瞬时CK通量。对于150 U/kg的CK剂量，稳态分布容积为0.050±0.0115 L/kg，血浆半衰期为112±18分钟。肌肉注射CK后，终末相半衰期为11.8±5.3小时，表明存在翻转过程，CK的平均生物利用度接近100%。肌肉注射PBZ后，CK活性显著增加，颈部给药后峰值为508±109 U/L，臀部给药后为873±365 U/L。通过测量受损肌肉释放的CK总量，计算出颈部注射PBZ后相当于0.044±0.029 g/kg的肌肉被破坏。臀内注射PBZ后相应数字为0.118±0.048 g/kg。通过对血浆CK活性进行反卷积分析，结果显示PBZ给药后最初30 - 60分钟CK进入速率最高，随后缓慢下降，在PBZ给药后24 - 48小时延迟后恢复到对照值。结论是，可控性肌肉损伤后的CK释放模式是一种用于量化受损肌肉量的非侵入性方法，并且通过反卷积计算CK输入速率对于描述肌肉细胞水平的事件具有潜在意义。
