Arterial and venous pharmacokinetics of intravenous heroin in subjects whoare addicted to narcotics

Citation
Km. Rentsch et al., Arterial and venous pharmacokinetics of intravenous heroin in subjects whoare addicted to narcotics, CLIN PHARM, 70(3), 2001, pp. 237-246
Citations number
24
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology,"Pharmacology & Toxicology
Journal title
CLINICAL PHARMACOLOGY & THERAPEUTICS
ISSN journal
0009-9236 → ACNP
Volume
70
Issue
3
Year of publication
2001
Pages
237 - 246
Database
ISI
SICI code
0009-9236(200109)70:3<237:AAVPOI>2.0.ZU;2-T
Abstract
Background: In Switzerland, medical prescription of heroin (diacetylmorphin e) is currently being evaluated as a treatment option for heavily dependent addicts. Therefore the diacetylmorphine pharmacokinetics in opioid-addicte d patients was studied. Methods: Three different diacetylmorphine doses (up to 210 mg) and 20 mg de uterium-labeled morphine (morphine-d3) were administered intravenously to 8 heroin-addicted patients. Arterial and venous plasma samples were collecte d, and diacetylmorphine, monoacetylmorphine, morphine, morphine-3-glucuroni de, morphine-6-glucuronide, and morphine-d3 plasma concentrations were meas ured by liquid chromatography-mass spectrometry. Results: Maximal arterial concentrations of diacetylmorphine, monoacetylmor phine, and morphine were 2.4, 5.4, and 1.4 times higher and occurred 2 to 3 minutes earlier than maximal venous concentrations. Venous areas under the concentration-time curves (AUC) of diacetylmorphine and monoacetylmorphine were 35% and 26% lower than arterial AUC values, whereas for morphine the venous AUC was 15% higher. Morphine-3-glucuronide and morphine-6-glucuronid e exhibited no arteriovenous differences. AUCs for diacetylmorphine, monoac etylmorphine, and morphine increased linearly with dose: Diacetylmorphine w as completely metabolized to morphine. Substantial morphine input into the arterial circulation persisted for up to 90 minutes. The arterial clearance s of diacetylmorphine, monoacetylmorphine, and morphine-d3 were 8.7 +/- 2.6 , 6.7 +/- 1.6, and 2.3 +/- 0.3 L/min, respectively. The arterial half-lives of diacetylmorphine and morphine-d3 were 2.4 +/- 0.8 and 88 +/- 21 minutes , respectively. Conclusions: These data indicate that substantial arteriovenous differences exist for diacetylmorphine and metabolite kinetics, that the pharmacokinet ics of diacetylmorphine and metabolites is linear even in the high dose ran ge used by opioid addicts, and that not only diacetylmorphine but also mono acetylmorphine is substantially metabolized peripherally to morphine.