Pharmacokinetics and Pharmacodynamics of Smoked Heroin*

Abstract

Despite the current popularity of smoking as a route of drug self-administration, there have been few human studies characterizing the pharmacokinetics and pharmacodynamics of smoked drugs of abuse. A variety of technological difficulties are encountered in the design of smoking studies, such as delivering reproducible doses and limiting the amount of pyrolysis of parent drug. As part of a concerted research effort to deliver precise, smoked doses of drug, a computer-assisted smoking device was utilized that delivered single puffs of heroin vapor to human subjects under controlled clinical conditions. Recovery studies indicated that the smoking device delivered approximately 89% of parent heroin to subjects. Although only two qualified heroin smokers could be identified as eligible volunteers, their participation provided the unique opportunity to study the pharmacokinetics and pharmacodynamics of smoked heroin. The two subjects were administered four smoked heroin doses in ascending order. In addition, four intravenous doses of heroin were administered for comparison of effects and estimation of bioavailability. Concurrent physiological, behavioral, and performance measures were collected along with blood samples. Blood was analyzed for heroin, 6-acetylmorphine, and morphine by solid-phase extraction gas chromatography-mass spectrometry. Heroin appeared rapidly in blood after administration and peaked 1-5 minutes after smoking, which is similar to that observed following intravenous administration. Heroin concentrations declined rapidly to the limit of detection (1.0 ng/mL) by 30 minutes. 6-Acetylmorphine blood concentrations also peaked and declined rapidly after smoked heroin with peak concentrations occurring at 1-2 minutes after smoking. Morphine levels rose and decayed more slowly. Mean elimination half-lives for heroin, 6-acetylmorphine, and morphine were 3.3 min, 5.4 min, and 18.8 min, respectively, by the smoked route. The bioavailability of smoked heroin was highly variable. Physiological measures such as pupil diameter demonstrated a counterclockwise hysteresis compared with heroin blood levels. The rapid onset of pharmacological effects together with the early appearance of heroin and metabolites in blood following smoked heroin demonstrated the effectiveness of this route of drug administration. It is evident that the smoking route enables individuals to obtain similar pharmacological effects as are produced by intravenous administration of heroin.

Postmortem redistribution of the heroin metabolites morphine and morphine-3-glucuronide in rabbits over 24 h

“…6-MAM was only detected in two matrices throughout the 24h duration of the experiment, vitreous humour and muscle. These are matrices which have previously been found to be particularly good for the investigation of 6-MAM in postmortem toxicological investigations as they lack esterase enzymes which continue to metabolise 6-MAM even after death [30,31]. Heart, liver, lung and kidney were the tissues that proved to be the least useful for the confirmation of heroin after death as at best only 1/3 of samples were positive for 6-MAM after death.…”

Fenêtres de détection des xénobiotiques dans le sang, les urines, la salive et les cheveux

“…La dose utilisée au début est d'environ 10 mg, mais les sujets tolérants peuvent utiliser jusqu'à 1 ou 2 grammes. La durée de détection de la morphine dans le sang (LDD 1 ng/mL) était de 20 heures après administration de 12 ou de 20 mg d'héroïne par voie intraveineuse chez un sujet (22). Après avoir fumé 10.5 mg d'héroïne, la durée de détection variait entre 22 minutes et 2 heures (22).…”

“…La durée de détection de la morphine dans le sang (LDD 1 ng/mL) était de 20 heures après administration de 12 ou de 20 mg d'héroïne par voie intraveineuse chez un sujet (22). Après avoir fumé 10.5 mg d'héroïne, la durée de détection variait entre 22 minutes et 2 heures (22). Après injection intramusculaire de 20 mg de morphine, elle était détectable (LDD 0.6 ng/mL) pendant 24 heures dans le plasma (23).…”

Chasing the elusive dragon: the need for better definition

“…Pickworth & Henningfield cite the research of Jenkins et al (1994) to support their conclusion that smoked and intravenous heroin caused broadly equivalent effects. This is at odds with reports from heroin users themselves (Griffiths et al, 1994) and it would also seem to be at odds with the decision of the great majority of heroin users in North America among whom injecting is almost universal.…”