PT  - JOURNAL ARTICLE
AU  - Masafumi Kumazaki
AU  - Hitoshi Ando
AU  - Kentarou Ushijima
AU  - Tomohiro Maekawa
AU  - Yuya Motosugi
AU  - Makoto Takada
AU  - Masato Tateishi
AU  - Akio Fujimura
TI  - Influence of Dosing Time on the Efficacy and Safety of Finasteride in Rats
AID  - 10.1124/jpet.111.182865
DP  - 2011 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 718--723
VI  - 338
IP  - 2
4099  - http://jpet.aspetjournals.org/content/338/2/718.short
4100  - http://jpet.aspetjournals.org/content/338/2/718.full
SO  - J Pharmacol Exp Ther2011 Aug 01; 338
AB  - Finasteride (FIN), a widely used medication for the treatment of androgen-dependent diseases, blocks the conversion of testosterone to a 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 the 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.