Avodart Metabolism and Energy Expenditure: What the Evidence Actually Shows
At a glance
- Drug / dutasteride 0.5 mg soft gelatin capsule (Avodart) [1]
- Main metabolizing enzymes / CYP3A4 and CYP3A5 [1]
- Terminal half-life / about 5 weeks at steady state [1]
- Time to steady state / 65% after 1 month, about 90% after 3 months [1]
- DHT effect / median serum DHT down 90% at 2 weeks and 94% at 1 year [1]
- Testosterone effect / median rise of about 19% to 26%, still within the physiologic range [1]
- Energy expenditure / not reported in the Avodart label [1]
- Approved use / symptomatic BPH; hair loss is off-label [1]
Does dutasteride affect energy expenditure?
The Avodart label reports hormone changes but no calorie-burn outcome. Median serum DHT fell 85% after 1 week and 90% after 2 weeks on 0.5 mg daily, and was 94% below baseline at 1 year [1]. Median serum testosterone rose about 19% to 26% but stayed within the physiologic range [1]. Whether those hormone shifts change energy expenditure in an individual man is not answered by these data.
Dutasteride does not bind the androgen receptor [1]. It lowers DHT by inhibiting both type 1 and type 2 5-alpha-reductase [1].
How is dutasteride metabolized?
The label states that dutasteride is extensively metabolized by CYP3A4 and CYP3A5 [1]. It is not metabolized by CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, or 2E1 [1]. The drug is excreted mainly in feces, with about 5% unchanged [1].
The terminal half-life is about 5 weeks at steady state [1]. Serum levels remain detectable above 0.1 ng/mL for up to 4 to 6 months after stopping [1]. The label says men treated with Avodart should not donate blood until at least 6 months after their last dose, to avoid giving dutasteride to a pregnant transfusion recipient [1].
What are dutasteride's pharmacokinetics?
The label dose is 0.5 mg once daily, swallowed whole, with or without food [1]. Dutasteride reaches peak serum levels about 2 to 3 hours after a dose [1]. Absolute bioavailability is about 60% [1]. Food lowers the peak by 10% to 15%, which the label calls not clinically significant [1]. Dutasteride is 99.0% bound to albumin and 96.6% bound to alpha-1 acid glycoprotein, with a volume of distribution of 300 to 500 L [1].
Steady state builds slowly. The label estimates 65% of steady state after 1 month and about 90% after 3 months [1]. The average steady-state serum concentration after 1 year of 0.5 mg daily was 40 ng/mL [1].
Do CYP3A4 inhibitors change dutasteride exposure?
The label says the effect of potent CYP3A4 inhibitors on dutasteride has not been studied, and it advises caution with potent, chronic CYP3A4 inhibitors such as ritonavir [1]. Verapamil and diltiazem decrease dutasteride clearance and raise exposure, but the change is not considered clinically significant and no dose adjustment is recommended [1].
Does dutasteride cause weight gain or change body composition?
Weight and body composition are not reported outcomes in the label's trial tables. In the pooled 2-year BPH trials, the adverse reactions reported more often than placebo in months 0 to 6 were impotence (4.7% vs 1.7%), decreased libido (3.0% vs 1.4%), ejaculation disorders (1.4% vs 0.5%), and breast disorders (0.5% vs 0.2%) [1].
Frequently asked questions
Does dutasteride slow metabolism or lower metabolic rate?
How long does dutasteride stay in the body?
Which enzymes break down dutasteride?
Do CYP3A4 inhibitors raise dutasteride levels?
Does dutasteride cause weight gain?
References
- U.S. National Library of Medicine, DailyMed. Avodart (dutasteride) soft gelatin capsules, Waylis Therapeutics prescribing information. Avodart (dutasteride) soft gelatin capsules, Waylis Therapeutics label