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 14C-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 (tmax 1.0 to 1.4 h). The terminal elimination half-life (t1/2 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 calculated from the AUC0-infinity values was found to be 43 and 60% after p.o. and s.c. treatment. The apparent volume of distribution (Vd) and the whole body clearance (Cl) of deramciclane after i.v. administration were 25.0 +/- 7.1 l/kg and 2.6 +/- 0.5 l/h/kg, respectively. The AUC0-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 metabolic conversion. The AUC0-infinity of N-desmethyl-deramciclane was 5.7%, compared to that of the parent compound after i.v. administration.
Lengyel
J
J
Semmelweis University of Medicine, Department of Pharmacokinetics, Budapest, Hungary.
Bojti
E
E
Bolehovszky
A
A
Grézal
G
G
Klebovich
I
I
Magyar
K
K
D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D001711:Biotransformation; D001892:Camphanes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003640:Dealkylation; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D011817:Rabbits
D014151:Anti-Anxiety Agents; D001892:Camphanes; C060555:deramciclane