Mast cell mediator tryptase levels after inhalation or intravenous administration of high doses pharmaceutically prepared heroin.
BACKGROUND
Opioids like morphine and heroin induce mast cell degranulation in vitro. The release of mast cell mediators like histamine and tryptase may lead to allergic symptoms. In this study it was investigated whether mast cell mediator release also occurs in vivo in addicted patients who participated in a heroin on medical prescription trial, and were under treatment with large doses of heroin in combination with methadone.


METHODS
Plasma levels of tryptase, a specific marker for mast cell degranulation, were measured by immuno-assay at baseline and 60 min after heroin administration. Heroin was administered either by intravenous injection (11 subjects) or by inhalation (nine subjects). Single heroin doses varied from 200 to 450 mg. Besides tryptase, the plasma concentrations of heroin, its metabolite morphine and methadone were measured.


RESULTS
After heroin injection, the mean tryptase plasma concentration increased dose dependently by on average 23.1% (95% CI 14.6-31.6%). After heroin inhalation, no tryptase release was observed. Heroin and morphine peak plasma concentrations were 3-5 times greater in heroin injectors than in inhalers. In heroin injectors, tryptase levels were related to morphine peak concentrations, but not to heroin concentrations. Tryptase plasma concentrations were not related to methadone levels. Mild allergic reactions were reported in five cases after intravenous heroin use, but not after inhalation.


CONCLUSIONS
This study revealed that mast cell mediator tryptase concentrations increase after intravenous heroin injection in chronic opioid users, but not after heroin inhalation. This may be explained by the higher Cmax levels of metabolite morphine that were achieved after injection than after inhalation. Although statistical significance was reached, the degree of mast cell degranulation after intravenous injection of heroin was mild, and did not lead to clinically relevant side effects in this group of opioid-tolerant subjects.
Rook
E J
EJ
Slotervaart Hospital, Department of Pharmacy and Pharmacology, Amsterdam, The Netherlands. ej.rook@cbg-meb.nl
van Zanten
A P
AP
Van den Brink
W
W
van Ree
J M
JM
Beijnen
J H
JH
D000280:Administration, Inhalation; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D003932:Heroin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008691:Methadone / Q000097:blood; D008875:Middle Aged; D009020:Morphine / Q000097:blood; D053802:Tryptases / Q000097:blood / Q000187:drug effects*
D003932:Heroin; D009020:Morphine; D053802:Tryptases; D008691:Methadone