morphine-3-glucuronide and Liver-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

Plasma morphine, morphine-3-glucuronide and morphine-6-glucuronide concentrations were measured (HPLC) in two children immediately before orthotopic liver transplantation and in the postoperative period. Both of the patients had end-stage hepatic failure, but one also had impaired renal function before operation and was oliguric during and after surgery. Both patients metabolized morphine rapidly, but in the patient with renal failure, the metabolites appeared to accumulate. Morphine has active metabolic products and the accumulation of these in patients with impaired renal function may lead to a clinically observable prolongation of its effect.

Topics: Child, Preschool; Diuresis; Female; Humans; Kidney; Kinetics; Liver Diseases; Liver Transplantation; Male; Morphine; Morphine Derivatives; Postoperative Period