Ketoconazole

Also Known As: Ketoconazole, Nizoral

Ketoconazole is a synthetic antifungal drug used to prevent and treat fungal skin infections, especially in immunocompromised patients such as those with AIDS or those on chemotherapy. Ketoconazole is sold commercially as an anti-dandruff shampoo, topical cream, and oral tablet.

Ketoconazole is very lipophilic, which leads to accumulation in fatty tissues. The less toxic and more effective triazole compounds fluconazole and itraconazole are sometimes prefered for internal use. Ketoconazole is best absorbed at highly acidic levels, so antacids or other causes of decreased stomach acid levels will lower the drug's absorption when taken orally. Absorption can be increased by taking it with an acidic beverage, such as cola.

Ketoconazole is usually prescribed for topical infections such as athlete's foot, ringworm, candidiasis (yeast infection or thrush), and jock itch. The over-the-counter shampoo version can also be used as a body wash for the treatment of tinea versicolor.[2][3] Ketoconazole is used to treat eumycetoma, the fungal form of mycetoma.

The side effects of ketoconazole are sometimes used to treat non-fungal problems. The decrease in testosterone caused by the drug makes it useful for treating prostate cancer and for preventing post-operative erections[4] following penile surgery. Another use is the suppression of glucocorticoid synthesis, where it is used in the treatment of Cushing's syndrome.[5] These side effects have also been studied for use in reducing depressive symptoms [6] and drug addiction;[7] however, it has not succeeded in either of these roles.[8][9]

Ketoconazole is also used in combination with other drugs such as zinc pyrithione in rinse-off products. The anti-dandruff shampoo is designed for people who have a more serious case of dandruff where symptoms include, but are not limited to constant non-stop flaking, and severe itchiness.

It is a pregnancy category C drug because animal testing has shown it to cause teratogenesis in high dosages. Until recently,[when?] there were two human test cases on record (both during the treatment of Cushing's syndrome)[10][11] and no adverse effects were reported, but this is not a broad enough data sample to draw any meaningful conclusions. A subsequent trial in Europe failed to show a risk to infants of mothers receiving ketoconazole.[12]

Some preliminary research suggests that ketoconazole shampoo may be beneficial in men suffering from androgenic alopecia. Support for this comes primarily from a single study in 1998 that compared ketoconazole 2% to the proven hair loss drug minoxidil 2% in men with androgenic alopecia.[13] In a sample of 27 men, "Hair density and size and proportion of anagen follicles were improved almost similarly by both ketoconazole and minoxidil regimens.", the men washed with ketoconazole 2% shampoo once every 2–4 days, leaving the shampoo on the scalp for 3–5 minutes before rinsing (as with the treatment of dandruff and seborrheic dermatitis).[13]

While ketoconazole's possible mechanism of action in hair loss is still unclear, the study speculated that both hormones and the immune system may act synergistically to cause injury to the hair follicle. Since ketoconazole effectively treats the malassezia fungus that commonly inhabits the scalp, the researchers hypothesized that it may help to reduce hair loss by reducing inflammation from the fungus, in addition to having a direct anti-inflammatory and an antiandrogen effect.

The researchers were guarded about the meaning of their results, saying that more rigorous studies on larger groups of men should be done to confirm the findings, both to evaluate the ideal dosage and formulation, and to assess the desirability of routine treatment in this condition. Although no further research in humans has been undertaken, there was a study on ketoconazole in 2005 that supported the existence of a stimulatory effect on hair growth, this time in mice.[14]

Although ketoconazole may be useful as a hair loss treatment, the shampoo is only FDA approved for the treatment of dandruff and seborrheic dermatitis of the scalp, since the FDA do not accept that there is enough evidence to market it for hair loss.[15]


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