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Plasma levels of morphine and morphine glucuronides in the treatment of cancer pain: relationship to renal function and route of administration

Citation

Peterson, GM and Randall, CTC and Paterson, J, Plasma levels of morphine and morphine glucuronides in the treatment of cancer pain: relationship to renal function and route of administration, European journal of clinical pharmacology, 38, (2) pp. 121-4. ISSN 0031-6970 (1990) [Refereed Article]

DOI: doi:10.1007/BF00265969

Abstract

There is growing evidence that renally-impaired patients receiving morphine therapy are at greater risk of developing opiate toxicity, due to the accumulation of an active metabolite, morphine-6-glucuronide (M6G), which is usually excreted by the kidneys. This study examined the relationships between morphine dosage, renal function, and trough plasma concentrations of morphine and its glucuronide metabolites in 21 patients (aged mean: 68.5 years: 11 males) receiving either oral or subcutaneous morphine for terminal cancer pain. The median daily morphine dosages (mg.kg-1) were: orally 1.87 (range 0.37-6.82) and subcutaneously 1.64 (range 0.22-3.60). The median plasma concentrations of morphine, morphine-3-glucuronide (M3G), and M6G (ng.ml-1) were: 36.0, 1035.2, and 142.3, respectively. The plasma concentrations of morphine, M3G and M6G were each significantly related to the daily morphine dosage (n = 21, Spearman r = 0.79, 0.91, and 0.88 respectively). Accumulation of the morphine glucuronides was dependent on renal function. The plasma concentrations of M3G and M6G, when divided by the morphine concentration, were significantly related to the calculated creatinine clearance of the patient. Patients receiving oral morphine had higher plasma concentration ratios of glucuronide/morphine than those receiving subcutaneous therapy, presumably due to first-pass glucuronidation. The results of this study confirm that accumulation of the pharmacologically active M6G is related to renal function, which probably explains the observation that morphine dosage requirements are generally reduced in patients with renal impairment.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Pharmacology and Pharmaceutical Sciences
Research Field:Clinical Pharmacology and Therapeutics
Objective Division:Health
Objective Group:Public Health (excl. Specific Population Health)
Objective Field:Public Health (excl. Specific Population Health) not elsewhere classified
Author:Peterson, GM (Professor Gregory Peterson)
Author:Randall, CTC (Mr Cameron Randall)
ID Code:111124
Year Published:1990
Web of Science® Times Cited:90
Deposited By:College Office - CHM
Deposited On:2016-08-31
Last Modified:2016-08-31
Downloads:0

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