Bicalutamide
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Bicalutamide
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| Systematic (IUPAC) name | |
| N-[4-cyano-3-(trifluoromethyl)phenyl]- 3-(4-fluorophenyl)sulfonyl-2- hydroxy-2-methyl- propanamide | |
| Identifiers | |
| CAS number | |
| ATC code | L02 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C18H14F4N2O4S |
| Mol. mass | 430.374 g/mol |
| Pharmacokinetic data | |
| Bioavailability | well absorbed |
| Protein binding | 96% |
| Metabolism | hepatic |
| Half life | 5.8 days |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
X(US) |
| Legal status |
℞ Prescription only |
| Routes | Oral |
Bicalutamide (marketed as Casodex, Cosudex, Calutide, Kalumid) is an oral non-steroidal anti-androgen for prostate cancer. It was first launched in 1995 as a combination treatment (with surgical or medical castration) for advanced prostate cancer and subsequently launched as monotherapy for the treatment of earlier stages of the disease.
It is marketed by AstraZeneca with the brand names Casodex and Cosudex. Bicalutamide is recommended 50 mg once daily in combination with an LHRH analogue or surgical castration.
Contents |
[edit] Description
Bicalutamide is an oral non-steroidal anti-androgen with the empirical formula C18H14N2O4F4S and is an off-white powder that is practically insoluble in water.
[edit] Indications and use
For the treatment of stage D2 metastatic prostate cancer in combination with a luteinizing hormone-releasing hormone analogue or as a monotherapy. Has been used in clinical trials for ovarian cancer.
[edit] Contraindications and precautions
Bicalutamide is contra-indicated in females and children and must not be given to any patient who has shown a hypersensitivity reaction to its use.
[edit] Adverse reactions
Adverse reactions include reproductive system and breast disorders, breast tenderness, gynaecomastia, hot flushes, gastrointestinal disorders, diarrhoea, nausea, hepatic changes (elevated levels of transaminases, jaundice), asthenia and pruritus.
To understand the physiologic effects of Bicalutamide on the body one must first understand the biological effects of Testosterone and androgens on the androgen receptors in the body.
Androgen receptors are present in very high concentrations in the tissues that form the external genitalia (penis and associated structures) such as the pelvic muscles and prostate, scrotum and testicles.
Before birth and during fetal development blocking the androgen receptor of a developing male fetus would prevent the development of the a penis causing the male infant to be born with female external genitalia (that is a vagina without a cervix or uterus, and clitoris. As well the testicles would remain undescended. During fetal development any male fetus who cannot respond at the cellular level to Testosterone, whether it is from taking an anti-androgen like Bicalutamide, or 5-alpha-reductase inhibitors, or is a male who has inherited a defective gene causing a defective androgen receptor or defective 5-alpha reductase enzyme and cannot produce dihydrotestosterone will will not develope a penis. Such males are usually phenotypically identified as a female at birth.
In adult males blocking the androgen receptors by Bicalutamide, and eliminating the effect of Testosterone and the other androgens from binding and stimulating the cellular effects of androgens, Bicalutamide will cause a decline in sperm count, infertility, and a sexual difficulties.
The effects of blocking the androgen receptors and blocking the effects of androgens in the body will have significant effects on the ability of a man to get to get and maintain an erection, resulting usually in profound impotence, and a dramatic reduction in the response to erectile dysfunction medications.
Blocking androgens receptors in the brain will eliminate the inhibition of Testosterone on the release of Luteinizing hormone (LH). Since the body will not detect any Testosterone/androgens and their will be a dramatic rise in Luteinizing hormone secretion resulting in a very significant rise in Testosterone and Estrogen levels.
Since Bicalutamide will block the effect of Testosterone on all tissues, there will be no response by the body to the increased androgen levels, but the rising sex hormone production will increase the Estrogen levels in the man to be much higher than they would be in a man who has not been taking Bicalutamide. The Estrogen levels will rise until they are high enough to suppress the release of LH which is causing the Estrogen and Testosterone levels to rise. This rise in Estrogen level stimulated by the blockade of the androgen receptor is why some of the side effects of Bicalutamide is breast tenderness and gynecomastia. As well other feminization effects will occur such as fat accumulation on the hips and thighs.
If Bicalutamide is combined with an LHRH analogue or surgical castration then the elevation of Estrogen levels will be prevented and the risks of excessive estrogen will be reduced. But blocking the rise in Estrogen levels will dramatically increase the bone loss and osteoporosis that will result from the effects of Bicalutamide blocking the actions of androgens in the bone. Since both Testosterone and Estrogens are essential for normal bone metabolism, reducing the positive stimulation of both androgens and estrogens on bone metabolism will definitely increase bone loss and osteoporosis.
Muscle, tendons, joints, bone, and connective tissues will also be affected resulting in a loss of physical strength, reduction in bone density, osteoporosis,etc. The effects of Bicalutamide's blockade of the bodies response to Testosterone will be the the opposite of what happen to a boys body at puberty when Testosterone levels rise and Testosterone start to exert there effect on muscle mass and sexual function. And the effects of taking Bicalutamide will essentially be equivalent to a severe form of male andropause since there will be no effect of Testosterone or any other androgen in the body.
[edit] External links
- Casodex, Cosudex (manufacturer's website)
- Bicalutamide (patient information)
