A NONINVASIVE AND QUANTITATIVE METHOD FOR THE STUDY OF TISSUE-INJURY CAUSED BY INTRAMUSCULAR INJECTION OF DRUGS IN HORSES

The present study was undertaken to measure the weight of muscle destr oyed by an intramuscular injection of phenylbutazone (PBZ) in horses. In six horses, CK disposition parameters were evaluated after intraven ous (i.v.) and intramuscular (i.m.) administration of a CK horse prepa ration. The same horses received PBZ, a potentially irritating agent, by i.v. and i.m. (neck and hindquarter) routes. Data were analysed usi ng compartmental approaches and instantaneous CK flux was calculated u sing a discrete deconvolution method. For a 150 U/kg CK dose, the stea dy-state volume of distribution was 0.050 +/- 0.0115 L/kg and the plas ma half-life was 112 +/- 18 min. After CK i.m. administration, the hal f-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 P BZ i.m. administration, the CK activity was significantly increased wi th peak values of 508 +/- 109 U/L after the neck administration and 87 3 +/- 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 a dministration in the neck. The corresponding figure was 0.118 +/- 0.04 8 g/kg after intragluteal PBZ administration. By deconvoluting plasma CK activity, it was shown that the CK entry rate was maximum for the f irst 30-60 min following PBZ administration, which then decreased slow ly to return to the control value after a delay of 24-48 h after PBZ a dministration. It was concluded that the CK release pattern following a controlled muscular damage was a non-invasive approach useful for qu antifying the amount of damaged muscle, and that the calculation of CK input rate by deconvolution was of potential interest in describing e vents at the muscle cell level.