Rhythmic variations of pharmacokinetic processes of cyproterone acetate inrabbits

A study about the influence of administration time on pharmacokinetics of C yproterone acetate in rabbits was performed. Thirty animals were distribute d in six groups, each corresponding to a different time: 2, 6, 10, 14, 18 a nd 22 hours after light onset (HALO). Rabbits received a single intravenous administration of 4 mg kg(-1) Cyproterone acetate. Blood samples were take n and processed by high performance liquid chromatography. Plasmatic data w ere fitted to a biexponential equation. Concentration at zero time (Co), co ncentration at zero time extrapolated from the distribution phase (A), hybr id constant for distribution phase and its half life, volume of the central compartment (V-c), volume of distribution at steady state (V-ss), constant s for transferring the drug from the central compartment to the exterior (K -10) and from the central to the peripheral compartment presented chronobio logical variations (p < 0.05) and were fitted to a cosine equation. The fol lowing parameters adjusted to circadian rhythms: Co (Acrophase: 1.72 HALO); A (Acrophase: 4.09 HALO); V-c (Acrophase: 11.92 HALO); V-ss (Acrophase: 10 .12 HALO) and K-10 (Acrophase: 3.59 HALO). It was concluded that pharmacoki netics of intravenously injected CPA in rabbits would behave in a different , though predictable, manner according to the animal's biological clock.