Relationship between plasma concentrations of morphine and its metabolites and pain in cancer patients.
OBJECTIVE
This study was undertaken to investigate the relationship between the plasma concentration of morphine, morphine-3-glucuronide and morphine-6-glucuronide and pain in cancer patients receiving oral morphine.


METHODS
The trough value of plasma concentrations of morphine and its metabolites were measured by high performance liquid chromatography using an ultraviolet detector. Using this assay system, the plasma concentrations of morphine, morphine-3-glucuronide and morphine-6-glucuronide in 26 cancer pain patients were measured and compared with pain intensity. The pain intensity was assessed at the time of blood sampling using the visual analog scale.


RESULTS
The trough value of morphine and morphine-6-glucuronide did not show a significant correlation with pain intensity by visual analog scale assessment, but morphine-3-glucuronide and the ratio of morphine-3-glucuronide/morphine showed a significantly positive correlation (r = 0.528, P = 0.006 and r = 0.671, P < 0.001, respectively). By dividing the group according to low (≤ median value) or high (> median value) VAS scores a significant difference was found between the two groups in morphine-3-glucuronide and the ratio of morphine-3-glucuronide/morphine (P = 0.045 and P = 0.007, respectively).


CONCLUSIONS
These results indicated that the level of morphine-3-glucuronide is related to the patient's perception of morphine effect, and the plasma concentration of morphine-3-glucuronide and the ratio of morphine-3-glucuronide/morphine indicated potency to assess clinical effect.
Sakurada
Tomoya
T
Department of Drug Information and Communication, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8675, Japan. sakurat@p.chiba-u.ac.jp
Takada
Shinya
S
Eguchi
Hisae
H
Izumi
Keishiro
K
Satoh
Nobunori
N
Ueda
Shiro
S
D000284:Administration, Oral; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism; D009022:Morphine Derivatives / Q000097:blood* / Q000378:metabolism; D009369:Neoplasms / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D010146:Pain / Q000097:blood* / Q000188:drug therapy / Q000209:etiology; D010147:Pain Measurement / Q000187:drug effects
D000701:Analgesics, Opioid; D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D009020:Morphine; C018108:morphine-3-glucuronide