Morphine and morphine metabolite kinetics in the rat brain as assessed by transcortical microdialysis.
Morphine (M), morphine 3-glucuronide (M3G) and morphine 6-glucuronide (M6G) were subcutaneously administered at 10 mg/kg in three groups of six awake rats. A transverse microdialysis probe was implanted in the brain cortex and dialysates were collected every 30 minutes for a period of 4 hours. Dialysates were measured by two different opiate radioimmunoassays. Maximum brain opiate concentrations, 41 +/- 10 ng/ml (M), 147 +/- 27 ng/ml (M3G), 177 +/- 43 ng/ml (M6G), were reached at the same Tmax, 0.75 h, and elimination half-lives ranged from 0.99 to 0.81 h for the 3 compounds. Kinetic parameters confirmed that penetration and elimination rates in the extracellular space of the rat brain cortex for the 2 hydrophilic M metabolites were similar to those of M. These results indicate for the first time that, in spite of their structural differences, glucuronide metabolites of M are capable of crossing the blood-brain-barrier (BBB) at the same rate as morphine does, but in higher amount.
Barjavel
M
M
INSERM Unité 26, Hôpital Fernand Widal, Paris.
Sandouk
P
P
Plotkine
M
M
Scherrmann
J M
JM
D000818:Animals; D001812:Blood-Brain Barrier; D002540:Cerebral Cortex / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009020:Morphine / Q000493:pharmacokinetics*; D009022:Morphine Derivatives / Q000493:pharmacokinetics*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley
D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D009020:Morphine; C018108:morphine-3-glucuronide