morphine-6-glucuronide and Kidney-Diseases

This article reviews the pharmacokinetics of heroin after intravenous, oral, intranasal, intramuscular and rectal application and after inhalation in humans, with a special focus on heroin maintenance therapy in heroin dependent patients. In heroin maintenance therapy high doses pharmaceutically prepared heroin (up to 1000 mg/day) are prescribed to chronic heroin dependents, who do not respond to conventional interventions such as methadone maintenance treatment. Possible drug-drug interactions with the hydrolysis of heroin into 6-monoacetylmorphine and morphine, the glucuronidation of morphine and interactions with drug transporting proteins are described. Since renal and hepatic impairment is common in the special population of heroin dependent patients, specific attention was paid on the impact of renal and hepatic impairment. Hepatic impairment did not seem to have a clinically relevant effect on the pharmacokinetics of heroin and its metabolites. However, some modest effects of renal impairment have been noted, and therefore control of the creatinine clearance during heroin-assisted treatment seems recommendable.

Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Drug Interactions; Heroin; Humans; Kidney Diseases; Liver Diseases; Morphine; Morphine Derivatives

In a systematic review of 57 studies with information on 1232 patients we examined the effect of age, renal impairment, route of administration, and method of analysis on the ratios of morphine-3-glucuronide:morphine (M3G:M) and morphine-6-glucuronide:morphine (M6G:M) and the relative concentrations of M3G and M6G. Across all studies the range of the ratios of metabolites to morphine was wide (0.001-504 for M3G:M, and 0-97 for M6G:M). Neonates produced morphine glucuronides at a lower rate than older children or adults. Metabolite ratios were higher in renal impairment. Routes of administration which avoided first pass metabolism (intravenous, transdermal, rectal, intramuscular, epidural and intrathecal) resulted in lower metabolite production than oral, buccal or sublingual. Metabolite production was similar for single and multiple dosing. There was no evidence of differences between methods of assay. There was a high correlation between the two glucuronide metabolites in spite of the different situations studied, supporting a single glucuronidating enzyme. Morphine was present in CSF at a fourfold higher concentration than the glucuronide metabolites.

Topics: Adult; Aging; Analgesics, Opioid; Child; Dose-Response Relationship, Drug; Drug Administration Routes; Humans; Infant, Newborn; Kidney Diseases; Morphine; Morphine Derivatives

Topics: Consciousness; Critical Care; Humans; Kidney Diseases; Morphine; Morphine Derivatives

Patients with impaired renal function may experience severe and prolonged respiratory depression when treated with morphine. This has been attributed to accumulation of the drug during renal failure. Three patients are described who had classical signs of intoxication with morphine in the absence of measurable quantities of morphine in the plasma. The observed clinical effect is attributed to accumulation of the pharmacologically active metabolite morphine-6-glucuronide, which is usually renally excreted. It is concluded that morphine does not accumulate in patients with renal failure but that accumulation of metabolites does occur. The previously reported observations of morphine accumulation during renal failure probably result from the use of radioimmunoassays that cannot distinguish between morphine and morphine-6-glucuronide. Thus the apparent morphine concentration measured with these assays in fact reflects the total quantity of morphine and morphine-6-glucuronide present.

Topics: Acute Kidney Injury; Adult; Aged; Female; Humans; Kidney; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Morphine; Morphine Derivatives; Respiratory Insufficiency

Topics: Humans; Kidney Diseases; Morphine; Morphine Derivatives

Topics: Humans; Kidney Diseases; Morphine; Morphine Derivatives