Pharmacokinetics of high doses of intramuscular and oral heroin in narcotic addicts

Details

Serval ID
serval:BIB_950E27040DFD
Type
Article: article from journal or magazin.
Collection
Publications
Title
Pharmacokinetics of high doses of intramuscular and oral heroin in narcotic addicts
Journal
Clin Pharmacol Ther
Author(s)
Girardin F., Rentsch K. M., Schwab M. A., Maggiorini M., Pauli-Magnus C., Kullak-Ublick G. A., Meier P. J., Fattinger K.
ISSN
0009-9236 (Print)
ISSN-L
0009-9236
Publication state
Published
Issued date
10/2003
Volume
74
Number
4
Pages
341-52
Language
english
Notes
Girardin, Francois
Rentsch, Katharina M
Schwab, Marc-Andre
Maggiorini, Marco
Pauli-Magnus, Christiane
Kullak-Ublick, Gerd A
Meier, Peter J
Fattinger, Karin
eng
Clinical Trial
Research Support, Non-U.S. Gov't
Clin Pharmacol Ther. 2003 Oct;74(4):341-52. doi: 10.1016/S0009-9236(03)00199-1.
Abstract
BACKGROUND: In several countries medical prescription of diacetylmorphine is currently being evaluated as a treatment option for heavily dependent narcotic addicts. Because of damaged veins, many patients administer diacetylmorphine intramuscularly or orally. Therefore we characterized the pharmacokinetics of intramuscular and oral diacetylmorphine in the high dose range usually required in narcotic addicts. METHODS: Three intramuscular doses, 3 oral doses, and 1 intravenous dose of diacetylmorphine and oral and intravenous test doses of deuterium-labeled morphine (morphine-N-methyl-d3 [morphine-d3]) were administered to 8 heroin-addicted patients. Arterial plasma concentrations of diacetylmorphine, monoacetylmorphine, morphine, morphine-3-glucuronide, morphine-6-glucuronide, and morphine-d3 were measured by liquid chromatography-mass spectrometry. RESULTS: Intramuscularly administered diacetylmorphine (</=200-250 mg) exhibited linear diacetylmorphine, monoacetylmorphine, and morphine kinetics and resulted in sustained diacetylmorphine exposures (bioavailability, 380% +/- 157% [mean +/- SD]) and in lower and delayed peak monoacetylmorphine and morphine concentrations as compared with intravenous administration. Oral diacetylmorphine (</=600 mg) yielded negligible systemic diacetylmorphine and monoacetylmorphine exposures but was associated with linear kinetics and high bioavailabilities for morphine (67% +/- 19%), morphine-3-glucuronide (205% +/- 52%), and morphine-6-glucuronide (180% +/- 61%). In addition, oral diacetylmorphine was absorbed more rapidly and to a greater extent than a concomitant test dose of morphine-d3. CONCLUSIONS: On the basis of the linear pharmacokinetics, the high bioavailability of intramuscular diacetylmorphine, and the rapid and extended morphine absorption from oral diacetylmorphine, the intramuscular and oral routes can be recommended as safe and feasible alternatives to the intravenous route for medical prescription of diacetylmorphine.
Keywords
Administration, Oral, Adult, Area Under Curve, Biological Availability, Female, Half-Life, *Heroin/administration & dosage/blood/pharmacokinetics, Heroin Dependence/*metabolism, Humans, Injections, Intramuscular, Injections, Intravenous, Male, Metabolic Clearance Rate, *Narcotics/administration & dosage/blood/pharmacokinetics
Pubmed
Create date
10/02/2021 13:24
Last modification date
11/02/2021 7:26
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