Nizoral
[Comparison of fluconazole and ketoconazole in the therapy of vaginal candidiasis by administration in two different oral doses]

[Article in Italian]

Bottino G, Menna C.

USL n. 35, Ospedale Civile di Giaveno.

The authors examined 20 patients affected by vaginal candidiasis and evaluated the efficacy and tolerability of treatment with Fluconazole in comparison with Ketoconazole, using two different doses of oral administration: Fluconazole, 150 mg in a single dose; Ketoconazole, 400 mg/die for 5 days. There were no significant differences in results; adverse effects were insignificant and the level of efficacy, which was the same in both cases, was high. In conclusion, both molecules are confirmed to be efficacious, although patients showed a preference for the single dose and for only one day of therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2374654&dopt=Abstract ketoconazole Nizoral



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[Ketoconazole in the treatment of ocular mycoses]

[Article in Russian]

Maichuk IuF, Karimov MK, Lapshina NA.

Ketoconazole (aronazole manufactured by Janssen Pharmaceutica, Belgium) was used in the therapy of 29 patients with mycoses of the organ of vision, 5 of these with mycotic canaliculitis, 5 with mycotic conjunctivitis, 13 with keratomycosis, and 6 with mycotic endophthalmitis. The patients were administered 1 tablet of oronazole (200 mg of ketoconazole) daily usually for 2-3 weeks. In 6 cases with severe keratomycoses ketoconazole emulsion was additionally administered 5-6 times daily into the eye (in drops). 19 patients (including all those with keratomycosis) were cured, in 5 cases the clinical status improved, in another 5 no effect was achieved. No side effects were recorded. These data are in accord with the literature reports on the high efficacy of ketoconazole in the treatment of mycotic involvement of the organ of vision and on the high antimycotic spectrum of this drug.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2378037&dopt=Abstract ketoconazole Nizoral



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Activity of ketoconazole derivatives against Leishmania mexicana amazonensis within mouse peritoneal macrophages.

Pirson P, Leclef B, Trouet A.

Medgenix Group, Fleurus, Belgium.

Imidazoles such as ketoconazole have proven antileishmanial activity, both in vitro and in vivo. New derivatives of ketoconazole have been synthesized in order to improve the therapeutic index and antileishmanial activity as assessed by mouse peritoneal macrophages infected with Leishmania mexicana amazonesis. Amino-acid derivatives of ketoconazole are at least 10 times more effective than ketoconazole in vitro, and the best effect is observed using the phenylalanyl-ketoconazole. Fatty acid derivatives, such as oleoyl-ketoconazole, also possess a greater therapeutic activity but to a lesser extent than amino-acid derivatives. Moreover, oleoyl-ketoconazole showed a remarkable property in terms of effective dose. Our results demonstrate the potential antileishmanial efficacy of some ketoconazole derivatives, and suggest that phenylalanyl-ketoconazole should be considered for experimental evaluation in animal models.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2383093&dopt=Abstract ketoconazole Nizoral



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Inhibition of hepatic metastasis from a human pancreatic adenocarcinoma (RWP-2) in the nude mouse by prostacyclin, forskolin, and ketoconazole.

Tzanakakis GN, Agarwal KC, Vezeridis MP.

Surgical Service Veterans Administration Medical Center, Providence, RI 02908.

Metastasis is a multistep phenomenon in which platelets appear to play an important role. This study examined several compounds for their effects on experimental hepatic metastasis and on human pancreatic tumor cell-platelet interactions. Prostacyclin (PGI2) and forskolin (stimulators of platelet adenylate cyclase) and ketoconazole (inhibitor of lipoxygenese and thromboxane synthetase) were used in order to investigate their effects on hepatic metastases from a human pancreatic tumor cell (RWP-2) in the nude mouse. The tumor cells were injected intrasplenically and the animals were divided into control, prostacyclin (PGI2 200 micrograms), forskolin (150 micrograms), and ketoconazole (180 micrograms) groups. All three drugs were administered intraperitoneally 30 minutes before and 24 hours after the tumor cell injections. Statistically significant differences were observed between control and treated groups in tumor surface area (P less than 0.001), percentage of liver surface area occupied by tumor (P less than 0.001), and number of tumor colonies (P less than 0.004 for prostacyclin, P less than 0.005 for forskolin, and P less than 0.001 for ketoconazole). These agents also strongly inhibited RWP-2-induced platelet aggregation in human platelet-rich plasma.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2404557&dopt=Abstract ketoconazole Nizoral



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Failure of ketoconazole as anti-androgen therapy in nonresectable primary hepatocellular carcinoma.

Gupta S, Korula J.

Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461.

Lacking a treatment for nonresectable hepatocellular carcinoma (HCC), we have utilized the androgen antagonist properties of ketoconazole in treating eight patients, seven men and one woman, with HCC, which, in view of a higher prevalence of HCC in men, seems to be androgen dependent. Response to treatment was determined by grading symptoms, serum alphafetoprotein, alteration in tumor size, and duration of survival. No patient had any significant side-effects from ketoconazole. No symptomatic improvement occurred, percent tumor size increased from 38.6 +/- 12, mean +/- SEM, to 44.4 +/- 12, and mean survival in six patients who were followed until death was less than 8 weeks from diagnosis. Anti-androgenic therapy with ketoconazole was not effective in any of these patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2466073&dopt=Abstract ketoconazole Nizoral



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Effects of acute and chronic ketoconazole administration on hypothalamo--pituitary--adrenal axis activity and brain corticotropin-releasing hormone.

Smagin GN, Goeders NE.

Department of Pharmacology and Therapeutics, LSU Health Sciences Center, P.O. Box 33932, 1501 Kings Hwy, Shreveport, LA 71130-3932, USA.

We have been investigating the effects of ketoconazole on cocaine reward in rats for several years now. However, we recently confirmed that ketoconazole-induced changes in cocaine self-administration and reinstatement do not always correspond with decreases in plasma corticosterone, which suggests that other mechanisms must be underlying the behavioral effects that we observe. This experiment was therefore designed to determine the effects of acute, repeated and chronic ketoconazole administration on corticotropin-releasing hormone (CRH) content in hypothalamic and extra-hypothalamic brain sites in rats following the same dosing regimen that we use in our behavioral studies. Although ketoconazole significantly increased the concentration of ACTH in trunk blood, there were no significant effects on plasma cortisol, corticosterone or testosterone. There was also a significant increase in CRH content in the median eminence after the acute administration of ketoconazole that just failed to reach statistical significance following repeated or chronic administration. However, acute, repeated and chronic treatment with ketoconazole each significantly increased CRH content in the medial prefrontal cortex (MPC), but did not consistently affect the peptide in any other brain region studied. Since the MPC and CRH have been implicated in the neurobiology of cocaine, CRH-induced alterations in dopaminergic neurotransmission may play an important role in this peptide's effects on cocaine responsiveness. Taken together with the results from previous studies, these data suggest that ketoconazole may affect cocaine reward, at least in part, through interactions with dopamine and CRH within the MPC.

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High-dose ketoconazole in advanced hormone-refractory prostate cancer: endocrinologic and clinical effects.

Trump DL, Havlin KH, Messing EM, Cummings KB, Lange PH, Jordan VC.

University of Wisconsin Clinical Cancer Center, Madison.

High-dose ketoconazole (400 mg orally three times a day) and physiologic replacement doses of glucocorticoids (hydrocortisone, 20 mg 8 AM, 10 mg 4 PM, and 8 PM) were administered to 38 patients with advanced prostatic cancer, refractory to at least initial testicular androgen deprivation. Thirty patients were completely evaluable; six were withdrawn due to possible ketoconazole-related toxicity and were considered drug failures. Two patients were unevaluable due to intercurrent therapy or inability to maintain follow-up. Ketoconazole was generally well tolerated. Mild or moderate nausea and vomiting occurred in 37% of patients, but required dose modification or discontinuation in only three patients; no hepatic damage was seen. Five of 36 patients (14%) responded to ketoconazole as determined by palpable or radiographic tumor mass reduction of 50% or greater and normalization of acid phosphatase or bone scan. Fifty percent of patients entered were stable at 90 days. Plasma androstenedione and dehydroepiandrosterone sulfate (DHEAS) were reduced markedly in almost all patients. Plasma testosterone (T) levels were low and remained unchanged, while gonadotropins were persistently elevated. Mean plasma ketoconazole content was 6.6 micrograms/mL after 28 days of therapy. While ketoconazole with hydrocortisone does suppress plasma androgens in advanced prostatic cancer patients, this infrequently causes regression of cancer that has progressed despite adequate testicular androgen ablation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2474059&dopt=Abstract ketoconazole Nizoral