Morphine and morphine metabolite kinetics in the rat brain as assessed by transcortical microdialysis

• Published in: Life sciences (1973) Vol. 55; no. 16; pp. 1301 - 1308
• Main Authors: Barjavel, M., Sandouk, P., Plotkine, M., Scherrmann, J-M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 1994
• Subjects: 3-glucuronide; 6-glucuronide; Animals; Blood-Brain Barrier; Cerebral Cortex - metabolism; Male; Microdialysis; morphine; Morphine - pharmacokinetics; Morphine Derivatives - pharmacokinetics; Radioimmunoassay; Rats; Rats, Sprague-Dawley; transcortical microdialysis; 3-glucuronide; 6-glucuronide; transcortical microdialysis; morphine
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/0024-3205(94)90069-8

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 T max, 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.