Morphine perfused rabbits: a tool for experiments in forensic entomotoxicology.
In order to establish an animal model for entomotoxicological studies, the kinetics of morphine elimination from blood after a single intravenous injection of morphine and the concentration of morphine in tissues following a continuous perfusion were studied. The aim of these experiments was to obtain controlled morphine tissue concentrations similar to those encountered in fatal human heroin overdoses. These tissues can be used as a food source for developing fly larvae in entomotoxicological studies. In the single injection experiment, seven rabbits were administered 1 or 2 mg/kg body weight of morphine chlorhydrate via the main ear artery. Blood samples of 200 microL were removed regularly via a catheter. Morphine concentration was determined using RIA techniques. Morphine was found to be first rapidly distributed and then slowly eliminated, following a two-exponential equation. Elimination of morphine from blood can be described as a two-compartment model. Constants of the equation were determined using the Kaleidagraph program. Using those constants, the main pharmacokinetics parameters were calculated. Results of these parameters showed the following: clearance from 13.3 to 16.2 L.h.1, half-life of the distribution phase from 0.6 to 0.9 min, and half-life of the elimination phase from 21 to 26 min. These results were used to calculate the rate of perfusion of morphine for rabbits to obtain desired, controlled, and constant concentrations of morphine in tissues. In the second experiment, three rabbits received a perfusion of morphine intravascularly at a rate of 2 mg/kg/h for a period of 3 h. These rabbits were sacrificed and analyses performed on several abdominal and thoracic organs. Results showed that the concentrations of morphine differed according to the organ analyzed, but were reproducible for organs between animals. These concentrations were similar to those normally encountered in cases of human death due to heroin overdoses.
Hédouin
V
V
Institut de Médecine Légale et de Médecine Sociale, Lille, France.
Bourel
B
B
Martin-Bouyer
L
L
Bécart
A
A
Tournel
G
G
Deveaux
M
M
Gosset
D
D
D000818:Animals; D005554:Forensic Medicine / Q000379:methods*; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007700:Kinetics; D009020:Morphine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009294:Narcotics / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits / Q000378:metabolism*; D011863:Radioimmunoassay; D014018:Tissue Distribution
D009294:Narcotics; D009020:Morphine