Finasteride (FIN), a widely used medication for the treatment of androgen-dependent diseases, blocks the conversion of testosterone to more potent androgen, dihydrotestosterone (DHT). In this study, we investigated a dosing-time dependent effect and safety of FIN in rats. Androgen receptor (AR) mRNA and nuclear protein levels exhibited clear daily rhythms with the peak during the dark period in the prostate and during the light period in the liver. Repeated oral administration of FIN (5 or 100 mg/kg) at 3 h after lights on (HALO) for 2 weeks decreased serum DHT concentration throughout a 24-h period, whereas the dosing of the agent at 15 HALO decreased its level only transiently even in the higher dose group. FIN caused laboratory abnormalities in the 3 HALO group, but not in the 15 HALO group. However, the effect of FIN on the prostate weight was not influenced by the dosing-time. These results suggest that safety, but not effect, of FIN depends on its dosing-time in rats. The dosing of FIN in the active period might be a rational dosage regimen, which is needed to be confirmed in human subjects.
- Received April 10, 2011.
- Revision received May 16, 2011.
- Accepted May 20, 2011.
- The American Society for Pharmacology and Experimental Therapeutics