Chronopharmacokinetic behaviour of cyproterone acetate in rabbits.
Cyproterone acetate (CPA) is an antiandrogenic compound that shows a rhythmic toxicologic behaviour. The purpose of this study was to determine whether CPA pharmacokinetics in the rabbit were influenced by the administration time of day. Previously synchronised rabbits received a single intravenous dose of 4 mg kg(-1) of CPA at two hours after light onset (2 HALO) and 14 hours (14 HALO) after light onset. The drug concentration in plasma samples was determined by high performance liquid chromatography. The mean concentrations in plasma were significantly higher (P<0.05) in 2 HALO than in 14 HALO animals at five, 15 and 30 minutes after dosing. Both plasma concentration profiles were fitted to two-compartment open models. Mean A, Vc and Vss differed significantly between 2 and 14 HALO dosage (P<0.005). Temporal variations in plasma protein binding, drug distribution and in drug elimination may play an important role in explaining these results.
Boggio
J C
JC
Cátedra de Farmacología, Facultad de Agronomía y Veterinaria, Universidad Nacional de Litoral, Esperanza, Argentine.
Encinas
T
T
Rodríguez
C
C
Vinagre
E
E
San Andrés
M D
MD
San Andrés
M I
MI
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002909:Chronobiology Phenomena; D002940:Circadian Rhythm; D017373:Cyproterone Acetate / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D003624:Darkness; D004334:Drug Administration Schedule; D006207:Half-Life; D007275:Injections, Intravenous; D008027:Light; D008657:Metabolic Clearance Rate; D011817:Rabbits
D017373:Cyproterone Acetate