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 intravenous (i.v.), oral and rectal diacetylmorphine (diamorphine, heroin, DAM) preparations were compared. METHOD: Two heroin-dependent patients participating in a heroin-assisted treatment program received single or repeated doses of 200 - 690 mg DAM i.v., orally (capsules, controlled-release tablets) and rectally. Plasma and urine profiles of DAM and metabolites were monitored by high-performance liquid chromatography and gas chromatography mass spectrometry, 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 was 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 were adequate to produce flash and high effects without any cardiovascular and respiratory side-effects nor withdrawal symptoms. CONCLUSIONS: Oral and rectal DAM should further be tested and validated on a wider patient group for the non-invasive, long-term application of high-dose DAM within heroin-assisted treatment programs as alternative to the harmful i.v. application.