title: Pharmacokinetics and pharmacokinetic variability of heroin and its metabolites: review of the literature.
abstract: 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.
authors.affiliation: Medicines Evaluation Board, The Hague, The Netherlands. apahu@slz.nl
authors.forename: Elisabeth J
authors.initials: EJ
authors.lastname: Rook
authors.forename: Alwin D R
authors.initials: AD
authors.lastname: Huitema
authors.forename: Wim
authors.initials: W
authors.lastname: van den Brink
authors.forename: Jan M
authors.initials: JM
authors.lastname: van Ree
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D004347:Drug Interactions; D003932:Heroin / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism; D009020:Morphine / Q000493:pharmacokinetics*; D009022:Morphine Derivatives / Q000493:pharmacokinetics*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D003932:Heroin; D009020:Morphine; C026979:6-O-monoacetylmorphine; C018108:morphine-3-glucuronide