Pharmacodynamics and pharmacokinetics of intravenously, orally and rectally administered diacetylmorphine in opioid dependents, a two-patient pilot study within a heroin-assisted treatment program

Objective: The pharmacokinetics and pharmacodynamics of high-dose intraveno us (i.v.), oral and rectal diacetylmorphine (diamorphine, heroin, DAM) prep arations were compared. Method: Two heroin-dependent patients participating in a heroin-assisted treatment program received single or repeated doses o f 200 - 690 mg DAM i.v., orally (capsules, controlled-release tablets) and rectally. Plasma and urine profiles of DAM and metabolites were monitored b y high-performance liquid chromatography and gas chromatography mass spectr ometry, flash and high effects by visual analog scaling (VAS). Results: DAM was only detectable in plasma after i.v, administration. With a t(1/2)beta of 1.3 - 2.2 min it was rapidly desacetylated to 6-acetylmorphine which wa s further metabolized to morphine and its 3- and 6-O-glucuronide. Morphine- 3-glucuronide was the dominating metabolite in plasma and urine independent of the administration route. Oral and rectal doses and dosage intervals we re adequate to produce flash and high effects without any cardiovascular an d respiratory side-effects nor withdrawal symptoms. Conclusions: Oral and r ectal DAM should further be tested and validated on a wider patient group f or the non-invasive, long-term application of high-dose DAM within heroin-a ssisted treatment programs as alternative to the harmful i.v. application.