Dutasteride vs. Finasteride
Dutasteride & Finasteride Mechanisms of Action
Dutasteride and finasteride are both 5-alpha-reductase (5AR) inhibitors. Both treatments work by inhibiting 5AR, the enzyme responsible for converting testosterone to dihydrotestosterone (DHT). DHT is the primary androgen in the prostate. It is a primary factor in the development and progression of benign prostatic hyperplasia (BPH) and other prostate diseases and is also a major cause of hair loss.
Dutasteride is a competitive inhibitor of both type-1 and type-2 isoenzymes of DHT, with 45-fold greater potency than finasteride against type-1 and type-2 isoenzymes. Approximately 85% to 90% of DHT is suppressed by the inhibition of type-2 isozymes. The remaining DHT is hypothesized to be from type-1 5-alpha-reductase. Finasteride is a competitive inhibitor of 5-alpha-reductase that selectively inhibits the type-2 isoenzyme. The dual inhibition resulting from dutasteride treatment may be beneficial in prostatic diseases that depend on androgens, as both isoenzymes are up-regulated in BPH while only the type-1 isoenzyme is up-regulated in prostate cancer. It is not yet known if there are clinical differences between selective inhibitors and dual inhibitors of 5-alpha-reductase in the treatment of BPH.
Effect of Dutasteride and Finasteride on Serum DHT Concentrations
Serum DHT suppression when taking dutasteride is significantly greater than Serum DHT suppression when taking finasteride. treatment with dutasteride (0.5mg daily) in patients with BPH resulted in median reductions in serum DHT concentrations of 94% after one year of treatment and 93% after two years of treatment. Therapy with Finasteride (5 mg daily) for up to 4 years in patients with BPH suppressed serum DHT concentrations by only 70%.
Treatment with dutasteride resulted in fast decrease in serum DHT concentrations. After one week of treatment serum DHT concentrations were reduced by 85% and by 90% after two weeks of treatment.
Dutasteride resulted in a greater suppression of DHT than finasteride and the response to dutasteride was less variable than finasteride in longer term-studies. After four months of treatment 0.5mg dutasteride reduced serum DHT concentration by 94.7% (+/- 3.3%) while 5mg finasteride decreased serum DHT concentrations by 70.8% (+/- 18.3%).
After treatment had been stopped, serum DHT concentrations returned to within 20% of baseline values 4 weeks following the end of treatment in those subjects taking finasteride and 16 weeks in those taking dutasteride.
Effect of dutasteride and finasteride on Serum Testorsterone
Dutasteride and finasteride both increase median circulating testosterone concentration. Increase of 10-20% from baseline values have been noted, however concentrations remained within normal physiologic limits.
Effect of Dutasteride and inasteride on Bone Density and Lipid Metabolism
Neither dutasteride nor finasteride resulted in significant changes in bone density or lipid metabolism.
Intraprostatic DHT Reduction with Dutasteride
In patients taking 5mg of dutasteride mean DHT concentrations in prostatic tissue were significantly lower (784 pg/g compared with 5793 pg/g with placebo).
In another study dutasteride was administered at 10mg daily for the initial 7 days followed by 5mg daily thereafter. Intraprostatic DHT values were 2.9% of those in placebo group - a 97.1% reduction in intraprostatic DHT when taking dutasteride.
It should be noted that both studies used doasges above what is recommended to treat BPH. No data is yet available for dosages approved for treatment of BPH.
Intraprostatic DHT Reduction with Finasteride
Patients with BPH were treated with finasteride 1 to 100 mg daily (one-fifth to 200 times the normal daily dosage) for 7-10 days prior to prostate surgery. Intraprostatic DHT concentrations through the entire dosage range of were approximately 80% lower than those in patients receiving placebo.
In a longer-term study, 1mg finasteride or 5mg finasteride daily was administered for 6-8 weeks. Intraprostatic DHT concentrations were reduced by approximately 80% in patients taking 1mg and 90% in patients receiving 5mg compared with placebo.
Pharmacokinetic Parameters of Dutasteride and Finasteride
| Dutasteride | Finasteride | |
|---|---|---|
| Bioavailablity | 59% | 63% |
| Protein Binding | ~ 99.5% | ~ 90% |
| Half-Life | 5 weeks | 6hrs - 15hrs |
| Metabolites | 6-beta-hydroxydutasteride (active) | Two metabolites with < 20% activity |
| Elimination | Fecal (~ 45%); Renal (~ 1%) | Biliary (57%); Renal (39%) |