Br J Clin Pharmacol. 2005 Mar;59(3):346-54.
Co-administration of ketoconazole with H-antagonists ebastine and loratadine in healthy subjects: pharmacokinetic and pharmacodynamic effects.
Chaikin P, Gillen MS, Malik M, Pentikis H, Rhodes GR, Roberts DJ.
Kyowa Pharmaceutical Inc., Princeton, New Jersey, USA.

Aims Two studies were conducted to evaluate the effects of coadministration of ketoconazole with two nonsedating antihistamines, ebastine and loratadine, on the QTc interval and on the pharmacokinetics of the antihistamines. Methods In both studies healthy male subjects (55 in one study and 62 in the other) were assigned to receive 5 days of antihistamine (ebastine 20 mg qd in one study, and loratadine 10 mg qd in the other) or placebo alone using a predetermined randomization schedule, followed by 8 days of concomitant ketoconazole 450 mg qd/antihistamine or ketoconazole 400 mg qd/placebo. Serial ECGs and blood sampling for drug analysis were performed at baseline and on study days 5 (at the end of monotherapy) and 13 (at the end of combination therapy). QT intervals were corrected for heart rate using the formula QTc = QT/RR(alpha) with special emphasis on individualized alpha values derived from each subject's own QT/RR relationship at baseline. Results No significant changes in QTc interval from baseline were observed after 5 days administration of ebastine, loratadine or placebo. Ketoconazole/placebo increased the mean QTc (95% CI) by 6.96 (3.31-10.62) ms in the ebastine study and by 7.52 (4.15-10.89) ms in the loratadine study. Mean QTc was statistically significantly increased during both ebastine/ketoconazole administration (12.21 ms; 7.39-17.03 ms) and loratadine/ketoconazole administration (10.68 ms; 6.15-15.21 ms) but these changes were not statistically significantly different from the increases seen with placebo/ketoconazole (6.96 ms; 3.31-10.62 ms), P = 0.08 ebastine study, (7.52 ms; 4.15-10.89 ms), P = 0.26 loratadine study). After the addition of ketoconazole, the mean area under the plasma concentration-time curve (AUC) for ebastine increased by 42.5 fold, and that of its metabolite carebastine by 1.4 fold. The mean AUC for loratadine increased by 4.5 fold and that of its metabolite desloratadine by 1.9 fold following administration of ketoconazole. No subjects were withdrawn because of ECG changes or drug-related adverse events. Conclusions Ketoconazole altered the pharmacokinetic profiles of both ebastine and loratadine although the effect was greater for the former drug. The coadministration of ebastine with ketoconazole resulted in a non significant mean increase of 5.25 ms (-0.65 to 11.15 ms) over ketoconazole with placebo (6.96 ms) while ketoconazole plus loratadine resulted in a nonsignificant mean increase of 3.16 ms (-2.73 to 8.68 ms) over ketoconazole plus placebo (7.52 ms). Changes in uncorrected QT intervals for both antihistamines were not statistically different from those observed with ketoconazole alone. The greater effect of ketoconazole on the pharmacokinetics of ebastine was not accompanied by a correspondingly greater pharmacodynamic effect on cardiac repolarization.

Int J Pharm. 2005 Mar 23;292(1-2):195-9. Epub 2005 Jan 20.
Microbiological assay of ketoconazole in shampoo.
Staub I, Schapoval EE, Bergold AM.
Programa de Pos-Graduacao em Ciencias Farmaceuticas, UFRGS, Av. Ipiranga 2752 Porto Alegre CEP 90610-000, Brasil.

Ketoconazole, an anti-fungal agent, is often incorporated in several pharmaceutical forms and in shampoo formulation it is known to be effective against fungal infection on the scalp. This paper describes a method to quantify ketoconazole in shampoo by comparing the cylinder plate assay and the HPLC method. The test organism used for the agar diffusion assay was Candida albicans ATCC 10231. Three different concentrations of ketoconazole were used for the diffusion assay. A mean zone diameter was obtained for each concentration. A standard curve was obtained by plotting the three values derived from the zone diameters. A prospective validation of the method showed that the method was linear (r=0.9982), precise (R.S.D.=2.57%) and accurate. The results obtained by the two methods were statistically evaluated by analysis of variance (ANOVA) and the results obtained indicate that there is no significant difference between these two methods.

Dermatol Clin. 2003 Jul;21(3):469-79, vi.
The use of oral antifungal agents to treat onychomycosis.
Gupta AK, Ryder JE.
Division of Dermatology, Department of Medicine, Sunnybrook and Women's College Health Science Center (Sunnybrook Site), University of Toronto, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada.

Onychomycosis has been treated for years with oral antifungal agents, and more recently in the United States with a topical nail lacquer. Griseofulvin was the first significant oral agent available to manage onychomycosis. The introduction of the azoles (ketoconazole, itraconazole, and fluconazole) and the allylamine, terbinafine, led to improved cure rates and a broad spectrum of activity. Pharmacokinetic studies have shown that the newer oral agents penetrate the nail within approximately one to two weeks after the start of therapy and remain for several months after the end of treatment. This article reviews the oral antifungal agents used to treat onychomycosis.

J Urol 2002 Oct;168(4 Pt 1):1583-8
Preclinical activity of ketoconazole in combination with calcitriol or the vitamin D analogue EB 1089 in prostate cancer cells.
Peehl DM, Seto E, Hsu JY, Feldman D
Department of Urology, Stanford University School of Medicine, California 94305-5118, USA

PURPOSE: Ketoconazole is a general inhibitor of P450 enzymes, of which some are necessary for androgen biosynthesis and the metabolism of vitamin D compounds. We tested the growth inhibitory activity of ketoconazole combined with 1,25-dihydroxyvitamin D3 (calcitriol) and with the vitamin D analogue EB 1089 in a preclinical model of prostate cancer. MATERIALS AND METHODS: Clonal assays with primary cultures of human prostatic cancer cells were performed to test anti-proliferative effects of ketoconazole alone or in combination with calcitriol or EB 1089. Enzyme substrate reactions were done to determine whether the ability of ketoconazole to potentiate the activity of calcitriol or EB 1089 was due to the inhibition of 25-hydroxyvitamin D3-24-hydroxylase (24-hydroxylase), the enzyme that initiates conversion of active vitamin D compounds to inactive products. RESULTS: Ketoconazole, calcitriol and EB 1089 each inhibited the growth of prostatic cancer cells. In combination 0.1 microg./ml. ketoconazole potentiated growth inhibitory activity of calcitriol 50-fold and EB 1089 10-fold. Induction of 24-hydroxylase by calcitriol or EB 1089 was partially blocked by this level of ketoconazole. CONCLUSIONS: Combination therapy with ketoconazole and calcitriol or EB 1089 may enhance antitumor activities of vitamin D compounds for prostate cancer and alleviate side effects of vitamin D deficiency that are likely associated with ketoconazole therapy.

Drug information

GENERIC NAME: ketoconazole
BRAND NAME: Nizoral

DRUG CLASS AND MECHANISM: Ketoconazole is an antifungal medication. Fungi are organisms normally found on the skin and in moist areas of the body. When the skin is injured or chronically moistened, or normal bacteria flora of the body are altered due to prolonged antibiotic treatment, fungus can proliferate to cause inflammation of the skin or moist body areas. Fungus organisms can also infect the lungs and other body tissues especially in patients with weakened immune systems.

PREPARATIONS: Tablets: 200 mg; Shampoo: 2%; Cream:2%.

STORAGE: Ketoconazole tablets: store at 59-86degrees F, protect from moisture. Ketaconazole shampoo: store at a temperature not above 77 degrees F, protect from light.

PRESCRIBED FOR: Ketoconazole is used to treat a variety of fungal infections. Examples of these fungal infections include candida infections of the skin or mouth (thrush), blastomycosis, histoplasmosis, coccidiomycosis, and others. Ketoconazole is also used to treat fungal infections that have not responded to griseofulvin, another antifungal medication.

DOSING: Ketoconazole may be taken with or without food. Ketoconazole tablets need the acidity of the stomach to dissolve. Therefore, ketoconazole should be administered at least two hours before taking antacids or acid-inhibiting medications (such as Tagamet or Zantac).

Ketoconazole should be avoided by patients with liver dysfunction. Signs of liver problems include unusual fatigue, loss of appetite, nausea and vomiting, yellowing of the skin (jaundice), dark urine, and pale stools. Development of these symptoms while taking ketoconazole should be reported to the physician.

DRUG INTERACTIONS: Ketoconazole should not be administered together with antihistamines terfenadine (Seldane) and astemizole (Hismanal), or with cisapride (Propulsid), because of increased risk of serious heart side effects. Ketoconazole should not be taken with the sedative triazolam (Halcion), because of risk of excessive sedation. Digoxin (Lanoxin) and phenytoin (Dilantin) levels should be monitored when taking ketoconazole. Tuberculosis medications INH and rifampin lower the blood levels of ketoconazole. Ketoconazole taken with alcohol can cause flushing, rash, swelling, headache, and nausea. Ketoconazole shampoo can irritate the eyes, and should be used with caution. Ketoconazole is avoided in children.

PREGNANCY: Ketoconazole is avoided during pregnancy.

NURSING MOTHERS: Ketoconazole is avoided in nursing mothers.

SIDE EFFECTS: Ketoconazole is generally well tolerated. Ketoconazole can cause rash, itching, nausea and/or vomiting, abdominal pain, headache, dizziness, fatigue, impotence, and blood count abnormalities. Rarely, ketoconazole has caused a reaction resulting in serious lowering of the blood pressure and shock (anaphylaxis). Also rarely, ketoconazole has caused severe depression, hair loss, and tingling sensations. Ketoconazole shampoo has been reported to result in loss of curl of permanently waved hair.

Caution! Before starting to take this medicine, it is vital that you should consult your doctor! Do not use it on your own initiative, without medical advice.
Also, you should read carefully important health information about this drug given here:

www.nlm.nih.gov

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NIZORAL
Generic name: Ketoconazole
Manufacturer: Janssen Pharmaceutica

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Dosage	Packing	Price	Pay now
200 mg	30 tab	USD 32.00
200 mg	90 tab	USD 89.00

NIZORAL 2 % cream
Generic name: Ketoconazole
Manufacturer: Janssen Pharmaceutica

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Dosage	Packing	Price	Pay now
45 g	3 Tubes	USD 19.00
90 g	6 Tubes	USD 47.00