In vivo non-invasive quantification of muscle damage following a single intramuscular injection of phenylbutazone in sheep.
Intramuscular drug administration can lead to more or less extensive muscle damage. The aim of the present study was to show the possibility of quantitating, in vivo and non-invasively, the equivalence of muscle destroyed by the administration of a test drug (phenylbutazone) known for its injurious properties. Creatine kinase (CK) kinetic parameters (clearance, volume of distribution) were measured in 6 sheep after an iv administration of muscle CK homogenate. In the same 6 sheep, CK release after iv and im 8 mg phenylbutazone/kg was measured. The calculated total CK released, based on the CK plasma clearance (0.28 mL/kg/min) and area under the curve of CK activity after im phenylbutazone administration was 191 +/- 140 U/kg. By relating this quantity to that of CK gluteal muscle (5114 +/- 891 U/g), it was calculated that im phenylbutazone administration was able to destroy an equivalence of 2.4 +/- 2.1 g of muscle. For the 2 main sites of im administration (neck and gluteal muscle), general equations are proposed to calculate the equivalence of muscle destroyed in sheep when only plasma CK activity following a test drug administration is available.
Houpert
P
P
Departement de Physiopathologie, Ecole Nationale Veterinaire, Toulouse, France.
Serthelon
J P
JP
Lefebvre
H P
HP
Toutain
P L
PL
Braun
J P
JP
D000818:Animals; D002081:Buttocks; D003402:Creatine Kinase / Q000097:blood / Q000378:metabolism*; D005260:Female; D007273:Injections, Intramuscular / Q000009:adverse effects / Q000662:veterinary*; D007275:Injections, Intravenous / Q000662:veterinary; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology; D009334:Neck Muscles / Q000187:drug effects; D010653:Phenylbutazone / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D012756:Sheep
D003402:Creatine Kinase; D010653:Phenylbutazone