Pharmacokinetics of deramciclane in rabbits

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.