Kk. Akerman et al., 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, Human psychopharmacology, 13(3), 1998, pp. 177-182
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.