The pharmacokinetics of deramciclane (CAS 120444-78-8, EGIS-3886) was inves
tigated in rabbits after i.v., p.o. and s.c. administration of 3 mg/kg C-14
-phenyl-deramciclane. The plasma concentration-time curves of total radioac
tivity, the parent compound (deramciclane) and its N-demethylated metabolit
e (EGIS-7056) were determined. The radioactivity level was measured by liqu
id scintillation technique while the concentration of the parent compound a
nd its metabolite was determined by gas chromatography-mass spectrometry de
tection. The p.o. and i.v. studies were carried out on the same group of an
imals, while a separate group of rabbits was used for studying s.c. absorpt
ion.
Deramciclane was readily absorbed after p.o. and s.c. treatment (t(max) 1.0
to 1.4 h). The terminal elimination half-life (t(1/2)(beta)) of the parent
compound fell between 5.8 to 7.1 h, while that of the total radioactivity
ranged from 21.6 and 26.0 h. The absolute bioavailability of deramciclane c
alculated from the AUC(0-infinity) values was found to be 43 and 60 % after
p.o. and s.c. treatment. The apparent volume of distribution (V-d) and the
whole body clearance (Cl) of deramciclane after i.v. administration were 2
5.0 +/- 7.1 1/kg and 2.6 +/- 0.5 1/h/kg, respectively. The AUC(0-infinity)
values of the parent compound varied between 4.6 and 7.9 % of that of total
radioactivity, suggesting that deramciclane was subjected to intensive met
abolic conversion. The AUC(0-infinity) of N-desmethyl-deramciclane was 5.7
%, compared to that of the parent compound after i.v. administration.