The Absolute Bioavailability of Rabbit Muscle Creatine Phosphokinase after Intramuscular Administration

  • 許 興智
    Department of Pharmaceutics, Chia Nan Jr. College of Pharmacy
  • 渡辺 淳
    Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Nagoya City University

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A two-period crossover study was carried out to determine the rate and the extent of bioavailability of rabbit muscle creatine phosphokinase (CPK) after intramuscular administration to six male rabbits. The plasma profile of CPK after intramuscular administration (500 U/kg body weight in 0.8 ml of 2% rabbit serum albumin solution into the vastus lateralis muscle) showed a plateau around 4-12 h. Intravenous administration of CPK was performed at doses of 300 and 500 U/kg body weight. The mean clearance/body weight and Vd_<ss>/body weight were 0.00604±0.00094 l/h/kg (mean±S.D., n=6) and 5.32±1.47%, respectively. The mean residence time (MRT_<im>) and mean absorption time (MAT_<im>) of CPK after intramuscular administration were 20.7±4.2 and 11.9±5.1 h, respectively. Since MAT_<im> was long relative to MRT_<im>, the rate of bioavailability was slow and the residence time distribution appeared to be skewed. The value of MAT_<im>/MRT_<im>, reflecting the contribution of moment of input function to the plasma activity of CPK, was 55.4±11.6%. The variance of residence time (VRT_<im>) and variance of absorption time (VAT_<im>) were 608±107 and 505±122h^2. The results imply that the aborption and disposition of CPK after intramuscular administration were rather complicated. The mean fraction of CPK absorbed was 0.311±0.149. Presumably, the incomplete access of CPK to the systemic circulation was due to extravascular inactivation.

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