4-OH-A
4-OH-A Uses, Dosage, Side Effects, Food Interaction and all others data.
4-OH-A was the first selective, type I, steroidal aromatase inhibitor used in the treatment of estrogen-receptor positive breast cancer in post-menopausal women. 4-OH-A suppresses estrogen production from anabolic steroids or prohormones. 4-OH-A is also a prohormone of 4-hydroxytestosterone, an active steroid with weak androgenic activity and mild aromatase inhibitor activity. It is listed as a prohibited substance by the World Anti-Doping Agency for use in athletes.
4-OH-A has poor oral bioavailability, and thus must be administered fortnightly (bi-weekly) by intramuscular injection. Some clinical data has suggested that the clinically recommended dose of 250mg was too low. With the discovery of newer, non-steroidal and steroidal, aromatase inhibitors which were orally active and less expensive than formestane, formestane lost popularity.
Currently, formestane (categorized as an anti-estrogenic agent) is prohibited from use in sports in accordance to the regulations of the World Anti-Doping Agency. It is not US FDA approved, and the intramuscular injection form of formestane (Lentaron) which was approved in Europe has been withdrawn.
| Trade Name | 4-OH-A |
| Generic | Formestane |
| Formestane Other Names | 4-hydroxyandrostenedione, 4-OH-A, 4-OHAD, Formestane, Formestano, Formestanum |
| Type | |
| Formula | C19H26O3 |
| Weight | Average: 302.4079 Monoisotopic: 302.188194698 |
| Groups | Approved, Investigational, Withdrawn |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
For the treatment of estrogen-receptor positive breast cancer in post-menopausal women.
How 4-OH-A works
4-OH-A is a second generation, irreversible, steroidal aromatase inhibitor. It inhibits the aromatase enzyme responsible for converting androgens to estrogens, thereby preventing estrogen production.
Breast cancer may be estrogen sensitive or insensitive. A majority of breast cancers are estrogen sensitive. Estrogen sensitive breast cancer cells depend on estrogen for viability. Thus removal of estrogen from the body can be an effective treatment for hormone sensitive breast cancers.
4-OH-A has been targeted specifically for the treatment of postmenopausal women. Unlike premenopausal women who produce most estrogen in the ovaries, postmenopausal women produce most estrogen in peripheral tissues with the help of the aromatase enzyme. 4-OH-A, an aromatase inhibitor, can thus help to decrease the local production of estrogen by blocking the aromatase enzyme in peripheral tissues (ie. adispose tissue of the breast) to treat hormone sensitive breast cancer.
Volume of Distribution
Vd = 1.8 L/kg; widely distributed to organs and tissues when delivered intravenously. [2]
Elimination Route
4-OH-A has poor oral bioavailability, but is fully bioavailable when administered via the established intramuscular route. The AUC after an intravenous pulse dose does not vary considerably from that of an intramuscular dose.
Within 24-48 h of the first dose of intramuscular formestane, a C(max) of 48.0 +/- 20.9 nmol/l was achieved in one study. [2]
Half Life
Terminal plasma elimination half life of 18 minutes, when delivered intravenously. [2]
Clearance
Plasma clearance is approximately 4.2 L/(h kg), when delivered intravenously.
In women, following a 500mg dose of formestane, 20% was excreted as glucuronide within the first 24 hours. [1]
One long term metabolite (3beta,4alpha-dihydroxy-5alpha-androstan-17-one) can be detected for 90 hours. A longer detection time is possible with more sensitive technology, which may be of utility in sports drug testing. [1]
Elimination Route
Renal elimination. >95% in urine, <5% in feces.
Innovators Monograph
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