Ketoconazole
Find information on thousands of medical conditions and prescription drugs.

Ketoconazole

Ketoconazole is a synthetic antifungal drug used to prevent and treat skin and fungal infections, especially in immunocompromised patients such as those with AIDS. Due to its side-effect profile, it has been superseded by newer antifungals, such as fluconazole and itraconazole. Ketoconazole is sold commercially as an anti-dandruff shampoo, branded Nizoral, by Janssen Pharmaceutica. more...

Home
Diseases
Medicines
A
B
C
D
E
F
G
H
I
J
K
Clonazepam
K-Dur
Kadian
Kainic acid
Kanamycin
Kantrex
Kariva
Kayexalate
Keflex
Kefzol
Kemstro
Keppra
Ketalar
Ketamine
Ketanserin
Ketek
Ketoconazole
Ketoprofen
Ketorolac
Ketotifen
Kionex
Klor-con
Klotrix
Konazol
Korostatin
Kytril
L
M
N
O
P
Q
R
S
T
U
V
W
X
Y
Z

Its CAS number is 65277-42-1 and its SMILES structure is CC(N1CCN(C2=CC=C (OC3()O (CN4C=CN=C4) (5=C(Cl)C=C(Cl)C=C5) OC3)C=C2)CC1)=O.

History

Ketoconazole was discovered in 1976 and released in the early 1980s, and was the first available oral treatment for fungal infections.

Usage

Ketoconazole is usually prescribed for infections such as athlete's foot, ringworm, candidiasis (yeast infection or thrush), jock itch. The over-the-counter shampoo version can also be used as a body wash for the treatment of tinea versicolor.

Ketoconazole is used to treat eumycetoma, the fungal form of mycetoma.

The side-effects of ketoconazole sometimes used to treat non-fungal problems. The decrease in testosterone caused by the drug makes it useful for treating prostate cancer. Another use is the suppression of glucocorticoid synthesis, where it is used in the treatment of Cushing's disease. These side effects have also been studied for use in reducing depressive symptoms and drug addiction; however, it has not succeded in either of these roles.

Ketoconazole can be prescribed as a 200-mg pill, a 2% ointment, or 2% shampoo for the treatment of dandruff or seborrhoeic dermatitis, or as a 1% over-the-counter shampoo (Nizoral).

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, severe itchiness, and the formation of a cold, sticky sweat on the scalp about one millimetre thick.

Ketoconazole is very lipophilic, which leads to accumulation in fatty tissues. The less toxic and more effective triazole compounds fluconazole and itraconazole have largely replaced ketoconazole 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 effectiveness when taken orally.

It is a pregnancy category C drug because animal testing has shown it to cause teratogenesis in high dosages. Only two human test cases have been recorded (both during the treatment of Cushing's syndrome) and no adverse effects were reported, but this is not a broad enough data sample to draw any meaningful conclusions.

Method of action

Ketoconazole is structurally similar to imidazole, and interferes with the fungal synthesis of ergosterol, the main constituent of cell membranes, as well as certain enzymes. It is specific for fungi, as mammalian cell membranes contain no ergosterol.

As with all azole antifungal agents, ketoconazole works principally by inhibition of an enzyme, cytochrome P450 14-alpha-demethylase (P45014DM). This enzyme is in the sterol biosynthesis pathway that leads from lanosterol to ergosterol. Fluconazole and itraconazole have been found to have a greater affinity for fungal cell membrane than ketoconazole, and thus lower doses of these azoles are required to kill fungi.

Read more at Wikipedia.org


[List your site here Free!]


In vitro susceptibility testing of ciclopirox, terbinafine, ketoconazole and itraconazole against dermatophytes and nondermatophytes, and in vitro evaluation
From Journal of Drugs in Dermatology, 12/1/03

Gupta AK, Kohli Y. Br J Dermatol 2003 Aug; 149(2):296-305.

The authors set out to determine the in vitro susceptibility of fungal organisms to ciclopirox, terbinafine, ketoconazole, and itraconazole, and to evaluate the in vitro activity and mode of interaction of ciclopirox in combination with either terbinafine or itraconazole. 133 strains were evaluated, including dermatophytes, Candida spp., and nondermatophyte molds. Some of the test medications had either additive, synergistic, or indifferent effects, but there were no cases of antagonism. The testing indicates that ciclopirox may have a broad antimicrobial profile including dermatophytes, yeasts, and other nondermatophytes. Terbinafine is extremely potent against dermatophytes. In vitro evaluation of activity of eiclopirox and terbinafine suggests many instances of synergy or additivism; for ciclopirox and itraconazole there may be indifference, synergy, or additivism.

JDD ARTICLE EVALUATION

In-vitro studies are a good start for any study, but once you see these organisms in-vivo you confront many complicating factors, such as competing bacteria, fungi, and environments. It would have been a more clinically relevant study if cultures of suspected patients (in-vivo) were performed and double-blinded studies involving the above medications were done. Some additive or synergistic effects are seen which can permit a lower dose of each of the medications; again, further studies are requires to recommend any therapies.

COPYRIGHT 2003 Journal of Drugs in Dermatology
COPYRIGHT 2004 Gale Group

Return to Ketoconazole
Home Contact Resources Exchange Links ebay