A non‐invasive and quantitative method for the study of tissue injury caused by intramuscular injection of drugs in horses

Abstract

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.