High levels of morphine-6-glucuronide in street heroin addicts.
BACKGROUND
In the body, heroin is rapidly transformed to 6-acetylmorphine (6-AM) and then to morphine, that in turn is mainly metabolized to morphine-3-glucuronide (M3G) and, at lesser extent, to morphine-6-glucuronide (M6G). Unlike M3G, M6G is a potent opioid agonist. Intravenous heroin abusers (IHU) are exposed to a wide array of drugs and contaminants that might affect glucuronidation.


OBJECTIVE
We assessed plasma and urine concentrations of M3G and M6G in four groups of subjects: the first two included long-term IHU either exposed to street heroin ( n=8) or receiving a single IV injection of morphine ( n=4), while the other two groups included non-IHU patients receiving acute IV ( n=8) or chronic oral ( n=6) administrations of morphine.


METHODS
After solid phase extraction plasma and urine concentrations of morphine metabolites were determined by HPLC analyses.


RESULTS
M3G accounted for the greater part of morphine glucuronides detected in body fluids of non-IHU patients treated with morphine. This pattern of metabolism remained stable across 15 days of oral administration of incremental doses of morphine. In contrast, the two groups of IHU (street heroin taking or morphine-treated subjects) showed a reduction of blood and urine M3G concentrations in favor of M6G. Consequently, M6G/M3G ratio was significantly higher in the two IHU groups in comparison with the non-IHU groups.


CONCLUSIONS
Chronic exposure to street heroin causes a relative increase in concentrations of the active metabolite, M6G. Since the pattern of M6G action seems closer to heroin than to morphine, the increased synthesis of M6G observed in IHU may prolong the narrow window of heroin effects.
Antonilli
Letizia
L
Dipartimento di Fisiologia Umana e Farmacologia Vittorio Erspamer, University of Rome La Sapienza and Policlinico Umberto I, P. le A. Moro 5, 00185, Rome, Italy.
Semeraro
Federico
F
Suriano
Carmen
C
Signore
Luciano
L
Nencini
Paolo
P
D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage; D000704:Analysis of Variance; D002851:Chromatography, High Pressure Liquid; D004334:Drug Administration Schedule; D005260:Female; D003932:Heroin / Q000008:administration & dosage; D006556:Heroin Dependence / Q000097:blood* / Q000652:urine*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage / Q000097:blood / Q000652:urine; D009022:Morphine Derivatives / Q000097:blood* / Q000652:urine*; D009294:Narcotics / Q000008:administration & dosage; D013997:Time Factors
D000701:Analgesics, Opioid; D009022:Morphine Derivatives; D009294:Narcotics; C035349:morphine-6-glucuronide; D003932:Heroin; D009020:Morphine; C018108:morphine-3-glucuronide