Pharmacokinetics of deramciclane in rabbits

The pharmacokinetics of deramciclane (CAS 120444-78-8, EGIS-3886) was investigated in rabbits after i.v., p.o. and s.c. administration of 3 mg/kg 14 C-phenyl-deramciclane. The plasma concentration-time curves of total radioactivity, the parent compound (deramciclane) and its N-demethylated metabolite (EGIS-7056) were determined. The radioactivity level was measured by liquid scintillation technique while the concentration of the parent compound and its metabolite was determined by gas chromatography-mass spectrometry detection. The p.o. and i.v. studies were carried out on the same group of animals, while a separate group of rabbits was used for studying S.C. absorption. 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 B ) 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 calculated from the AUC 0- ∞ 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 25.0 ± 7.1 I/kg and 2.6 ± 0.5 l/h/kg, respectively. The AUC 0- ∞ values of the parent compound varied between 4.6 and 7.9 % of that of total radioactivity, suggesting that deramciclane was subjected to intensive metabolic conversion. The AUC 0- ∞ of N-desmethyl-deramciclane was 5.7 %, compared to that of the parent compound after i.v. administration.