Serum and urine concentrations of morphine and morphine metabolites in patients with advanced cancer receiving continuous intravenous morphine: an observational study.
BACKGROUND
The feasibility and clinical implication of drug monitoring of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) need further investigation. This study aimed to determine what predicts serum concentrations of morphine in cancer patients receiving continuously intravenous morphine, the relationships between serum concentration of morphine/its metabolites and urinary concentrations, and the relation between morphine concentrations and with clinical outcomes.


METHODS
We collected serum and urine samples from 24 patients with advanced cancer undergoing continuously intravenous morphine therapy. Serum samples were obtained at day one. Spot urine samples were collected once daily on three consecutive days. Pain and adverse drug events were assessed using the Korean version of MD Anderson Symptom Inventory.


RESULTS
A total of 96 samples (72 urine and 24 serum samples) were collected. Median dose of morphine was 82.0 mg/24 h. In a multivariate analysis, total daily morphine dose was the most significant predictors of both serum and urine concentration of morphine. Morphine, M6G, and M3G in serum and urine were statistical significantly correlated (correlation coefficient = 0.81, 0.44, 0.56; p values < 0.01, 0.03, 0.01, respectively).


CONCLUSIONS
Spot urine concentrations of morphine and its metabolites were highly correlated to those of serum. Total dose of daily morphine was related to both serum and urine concentration of morphine and its metabolites.
Department of Palliative Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea. sharp1003@hanmail.net.
Yong Joo
YJ
Lee
Department of Medicine, Dongguk University School of Medicine, 30 Pildong-ro 1-gil, Jung-gu, Seoul, 100-715, South Korea. lisasuhmd@hotmail.com.
Sang-Yeon
SY
Suh
Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, South Korea. songjhcp@gmail.com.
Junghan
J
Song
Department of Statistics, Dongguk University, Seoul, South Korea. yms159133@hotmail.com.
Sanghee Shiny
SS
Lee
Department of Statistics, Dongguk University, Seoul, South Korea. aaahram@naver.com.
Ah-Ram
AR
Seo
Department of Statistics, Dongguk University, Seoul, South Korea. ahn@dongguk.edu.
Hong-Yup
HY
Ahn
Division of Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea. angelamd@catholic.ac.kr.
Myung Ah
MA
Lee
Department of Family Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea. musofm@catholic.ac.kr.
Chul-Min
CM
Kim
Departments of Anaesthesiology and Intensive Care Medicine, St. Olvas University Hospital, Trondheim, Norway. pal.klepstad@ntnu.no.|Department of Circulation and Medical Imaging, Medical Faculty, Norwegian University of Technology and Science, Trondheim, Norway. pal.klepstad@ntnu.no.
Pål
P
Klepstad
D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000097:blood* / Q000378:metabolism / Q000494:pharmacology / Q000652:urine; D009022:Morphine Derivatives / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy*; D056910:Republic of Korea
D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D009020:Morphine; C018108:morphine-3-glucuronide