When heroin was administered orally or rectally, no heroin or 6-monoacetylmorphine could be detected in plasma [31,44,48]. Consequently no “flash” was achieved after oral administration, although a sustained period of mild euphoria was reported. Probably hydrolysis of heroin into morphin occurred under the alkaline conditions of the duodenum and colon before absorption. Moreover, heroin could be subject of the first pass effect by esterases in the liver. The intravenous/oral AUC ratio of the metabolite morphin varied between the 50 and 67 % in different studies, which is comparable with oral morphine administration [31,48]. The first pass mechanism by the liver is avoided to a high extent after application of a heroin suppository, resulting in a lower M3G/morphine ratio after rectal administration (1.5-2.9) than after oral administration of heroin (4.6-12.3) [31,62] Scores on euphoria were significantly higher after rectal application than after an equal oral heroin dose [31].
