Dutasteride, sold under the brand name Avodart among others, is a medication primarily used to treat the symptoms of a benign prostatic hyperplasia (BPH), an enlarged prostate not associated with cancer. A few months may be required before benefits occur. It is also used for scalp hair loss in men and as a part of hormone therapy in transgender women. It is usually taken by mouth.
side effects
The most commonly reported side effects of dutasteride, although rare, include sexual dysfunction and depression. In the largest available study of 6,729 men with BPH, 9% experienced erectile dysfunction (compared to 5.7% treated with a placebo), 3.3% experienced decreased sex drive (vs 1.6% of placebo), and 1.9% had enlarged breasts (vs 1% of placebo). Exposure during pregnancy is specifically contraindicated because antiandrogens such as dutasteride have been shown to interfere with the sexual development of male fetuses.
Dutasteride was patented in 1993 by GlaxoSmithKline and was approved for medical use in 2001. In the United States and elsewhere, it is available as a generic medication. In 2018, it was the 291st-most commonly prescribed medication in the US with more than 1 million prescriptions.
Description
Dutasteride powder is a synthetic 4-azasteroid compound. It is a dual inhibitor of type 1 and 2 isoforms of 5α-reductase unlike finasteride, the first marketed 5α-reductase inhibitor, which only acts on type 2 isozyme. Dutasteride is a 3-fold greater inhibitor of type-2 5α-reductase than finasteride in men and has greater effect on the type-l than on type-2 isozyme. In animal models,dutasteride exhibited superior efficacy and pharmacokinetics compared to finasteride.
In patients with benign prostate hyperplasia, administration of dutasteride was shown to dose-dependently decrease serum dihydrotestosterone levels with greater efficacy as compared to finasteride (95% vs 67%). Serum testosterone levels increased with both active drugs, in conjunction with dihydrotestosterone suppression but remained within normal ranges. In long term studies, in men with moderate to severe benign prostate hyperplasia, once daily dutasteride significantly reduced prostate volume, reduced the risk of acute urinary retention and surgery by 57% and improved lower urinary tract symptoms and urinary flow measurements.
Chemical Properties
Dutasteride is a white to pale yellow powder It is soluble in ethanol (44 mg/mL), methanol (64 mg/mL), and polyethylene glycol 400 (3 mg/mL), but it is insoluble in water.
Uses Dutasteride is a dual inhibitor of 5a-reductase isoenzymes type 1 and 2; structurally related to Finasteride. Dutasteride is used in the treatment of benign prostatic hyperplasia. Dutasteride is associated with a low rate of transient serum aminotransferase elevations, but has yet to be linked to instances of clinically apparent acute liver injury.
Definition ChEBI: Dutasteride is an aza-steroid that is inasteride in which the tert-butyl group is replaced by a 2,5-bis(trifluoromethyl)phenyl group. A synthetic 4-azasteroid, dutasteride is a selective inhibitor of both the type 1 and type 2 isoforms of steroid 5alpha-reductase, an intracellular enzyme that converts testosterone to 5alpha-dihydrotestosterone. Dutasteride is used for the treatment of symptomatic benign prostatic hyperplasia in men with an enlarged prostate gland. It has a role as an EC 1.3.1.22 [3-oxo-5alpha-steroid 4-dehydrogenase (NADP(+))] inhibitor and an antihyperplasia drug. And is an aza-steroid, a member of (trifluoromethyl)benzenes and a delta-lactam. It derives from a hydride of a 5alpha-androstane.
Biological Functions
Similar to finasteride, dutasteride is a competitive and mechanism-based inhibitor not only of type 2 but also of type 1 5α-reductase isoenzymes, with which stable enzyme-NADP adduct complexes are formed, inhibiting the conversion of testosterone to DHT. The suppression of both type 1 and type 2 isoforms results in greater and more consistent reduction of plasma DHT than that observed for finasteride. The more effective dual inhibition of type 1 and type 2 5α-reductase isoforms lowers circulating DHT to a greater extent than with finasteride and shows advantages in treating BPH and other disease states (e.g., prostate cancer) that are DHT-dependent.
Biochem/physiol Actions Dutasteride is a potent dual inhibitor of 5α-reductase isoenzymes types 1 and 2 (IC50 = 6 nM 5-AR1; 7 nM 5-AR2). Dutasteride blocks testosterone conversion to dihydrotesterone, and is used clinically for treating benign prostatic hyperplasia (BPH).
Duta is the first and only double 5α reductase inhibitor used to treat Benign prostatic hyperplasia, and it is mainly used clinically to treat prostate enlargement, male-pattern hair loss, seborrheic hair loss, and hereditary hair loss.
dutasteride Side effects
The main side effects are ED, decreased libido, gynecomastia, and ejaculation disorders. Long-term use (>4 years), however, did not reveal increased onset of sexual side effects. In addition, the combination of dutasteride and tamsulosin is well-tolerated and has the added advantage of rapid symptomatic relief.dutasteride hair loss
Mode of action The human body contains type I and type II 5α reductase, with type II found mainly in the prostate, and type I found mainly in the liver and skin. 5α reductase is the main cause for continuous benign prostate enlargement; it promotes the transformation of testosterone in patients’ prostate into the more active dihydrotestosterone, thus causing prostate cells to enlarge and the prostate to swell. Dutasteride can inhibit both type I and II 5α reductase at the same time. This type of simultaneous inhibiting mechanism can rapidly and continuously reduce prostate size, dramatically improve urination, and reduce the risk fo acute urinary retention and its related prostate surgeries.
Melting point 242-250°C
Boiling point 620.3±55.0 °C(Predicted)
density 1.303±0.06 g/cm3(Predicted)
storage temp. -20°C
solubility DMSO: soluble2mg/mL, clear
pka 13.32±0.70(Predicted)
form powder
color white to beige
optical activity [α]/D +18 to +24°, c = 1 in chloroform-d
BCS Class 2/4
InChIKey JWJOTENAMICLJG-QWBYCMEYSA-N
SMILES N1[C@@]2([H])[C@@](C)([C@@]3([H])CC[C@@]4(C)[C@]([H])([C@]3([H])CC2)CC[C@@H]4C(NC2=CC(C(F)(F)F)=CC=C2C(F)(F)F)=O)C=CC1=O
More Introduction:https://en.wikipedia.org/wiki/Dutasteride
