Morphine-6-glucuronide concentrations and opioid-related side effects: a survey in cancer patients.
The active morphine metabolite, morphine-6-glucuronide (M-6-G), may contribute to both the analgesia and the adverse effects observed during morphine (MOR) therapy. To evaluate the relationship between M-6-G and adverse effects, we measured steady-state plasma concentrations of MOR and M-6-G and concurrently noted the presence or absence of moderate to severe cognitive impairment or myoclonus in 109 cancer patients who were receiving either oral (n = 71) or parenteral (n = 38) morphine. MOR and M-6-G plasma concentrations were determined by HPLC with electrochemical detection. The presence of cognitive impairment or myoclonus was analyzed in relation to molar M-6-G/MOR ratio, age, morphine dose, the use of other centrally acting drugs, renal function (blood urea nitrogen (BUN) and serum creatinine), hepatic function (serum bilirubin, serum glutamic oxalacetic transaminase (SGOT), and alkaline phosphotase) and serum lactate dehydrogenase (LDH). The patient population consisted of 60 women and 49 men. The mean age was 51.5 years (range: 10-85 years). The mean morphine dose (total dose-prior 48 h) was 486 mg (range: 40-4800 mg) for the oral group and 931 mg (range: (10-9062 mg) for the parenteral group. The mean molar M-6-G/MOR ratios were 6.1 (SD: 18.2; range: 0.01-153.3) for the oral treatment group and 2.7 (SD: 4.16; range: 0.05-23.8) for the parenteral treatment group. Overall, the M-6-G/MOR ratio demonstrated a moderate but significant correlation with BUN (r = 0.4; P < 0.001) and creatinine (r = 0.45; P < 0.001) levels, but not with the other clinical variables examined.(ABSTRACT TRUNCATED AT 250 WORDS)
Tiseo
Paul J
PJ
Pain Service, Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 USA Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 USA Department of Neurology, Cornell University Medical College, New York, NY 10021 USA Department of Pharmacology, Cornell University Medical College, New York, NY 10021 USA.
Thaler
Howard T
HT
Lapin
Jeanne
J
Inturrisi
Charles E
CE
Portenoy
Russell K
RK
Foley
Kathleen M
KM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D003072:Cognition Disorders / Q000139:chemically induced*; D004333:Drug Administration Routes; D005069:Evaluation Studies as Topic; D005260:Female; D006306:Health Surveys; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000009:adverse effects* / Q000097:blood; D009022:Morphine Derivatives / Q000009:adverse effects* / Q000097:blood; D009207:Myoclonus / Q000139:chemically induced; D009369:Neoplasms / Q000097:blood / Q000150:complications* / Q000523:psychology; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D012044:Regression Analysis
D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D009020:Morphine