PT  - JOURNAL ARTICLE
AU  - Dafang Wu
AU  - Young-Sook Kang
AU  - Ulrich Bickel
AU  - William M. Pardridge
TI  - Blood-Brain Barrier Permeability to Morphine-6-Glucuronide is Markedly Reduced Compared with Morphine
DP  - 1997 Jun 01
TA  - Drug Metabolism and Disposition
PG  - 768--771
VI  - 25
IP  - 6
4099  - http://dmd.aspetjournals.org/content/25/6/768.short
4100  - http://dmd.aspetjournals.org/content/25/6/768.full
SO  - Drug Metab Dispos1997 Jun 01; 25
AB  - The blood-brain barrier (BBB) permeability to morphine and morphine-6-glucuronide (M6G) is measured under identical conditions using an intravenous injection method in the rat and HPLC separation of morphine from its metabolites. The brain uptake of M6G expressed as %ID/g was 32-fold lower than that of morphine, and the BBB permeability surface area product (PS) of M6G was 57-fold lower as compared with that of morphine. Consistent with these in vivo data, the 1-octanol/buffer partition study showed the liposolubility of M6G was 187-fold lower than that of morphine. The CNS origin of M6G analgesia after peripheral administration was confirmed because the analgesia was completely blocked by naloxone, which crosses BBB, but not by naloxone methiodide, which does not enter brain from blood. In conclusion, the BBB permeability to M6G is markedly reduced as compared with morphine, consistent with the much lower lipid solubility of M6G relative to morphine. The American Society for Pharmacology and Experimental Therapeutics