THE METABOLISM OF I-123 LABELED -METHYL-6-OXO-4H-IMIDAZO[1,5-A][1,4]BENZODIAZEPINE (NNC13-8241) MEASURED IN HUMAN PLASMA IS ONLY MINOR

The imidazobenzodiazepine derivate I-123-labelled methyl-6-oxo-4H-imid azo[1,5-a][1,4]-benzodiazepine (NNC 13-8241) is a partial benzodiazepi ne agonist and binds with a high affinity to the benzodiazepine recept or. The favourable kinetic properties indicate that [I-123]NNC 13-8241 is a promising SPET ligand. In the present study, an extensive examin ation of the metabolite pattern of [I-123]NNC 13-8241 in plasma and ur ine from seven healthy subjects was performed using gradient HPLC. Aft er injection of [I-123]NNC 13-8241 into human beings, only one radioac tive metabolite was found in plasma 3-300 min post injection. This pol ar metabolite eluted together with the solvent front fraction. The pro portion of unchanged [I-123]NNC 13-8241 was 82-86 per cent during the entire study. In addition, two other radioactive metabolites were foun d in urine. The first metabolite was lipophilic and eluted slightly be fore the parent compound [I-123]NNC 13-8241. The second metabolite elu ted slightly after solvent front peak. The amount of unchanged [I-123] NNC 13-8241 in human urine was 9 per cent and the solvent front fracti on contained 72 per cent of total radioactivity. No detectable radioac tivity appeared with the same retention time as synthetisized nor-NNC 13-8241 in plasma or urine, which excludes the possibility of in vivo demethylation of [I-123]NNC 13-8241. In conclusion, the [I-123]NNC 13- 8241 was found to have only a minor metabolism, which favours its use as a SPET tracer for quantitation of the benzodiazepine receptor. (C) 1998 John Wiley & Sons, Ltd.