Nizoral
Ketoconazole-induced hepatic lysosomal phospholipidosis: the effect of concurrent barbiturate treatment.

Pakuts AP, Parks RJ, Paul CJ, Bujaki SJ, Mueller RW.

Health Protection Branch, Bureau of Drug Research, Drug Toxicology Division, Ottawa, Ontario, Canada.

An unusual hepatic phospholipidosis produced by repeated high doses of ketoconazole in the mouse was investigated. This abnormal phospholipid accumulation was dose dependent after seven days of daily oral treatment over a 150-350 mg/kg ketoconazole dose range. The accumulation continued after 21 days at the 250 mg/kg dose level. Ultrastructural and biochemical studies revealed that ketoconazole produced a hepatic lysosomal accumulation of concentric lamellar bodies, as typically produced by many cationic amphiphilic drugs. Ketoconazole administered orally in mice at 250 mg/kg also induced total hepatic protein, microsomal protein, cytochrome p-450, and ethylmorphine N-demethylation. Concurrent phenobarbital and ketoconazole administration appeared to further increase hepatic drug metabolizing parameters and to reduce the extent of the hepatic phospholipid accumulation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2326549&dopt=Abstract ketoconazole Nizoral



Nizoral
Neuroendocrinological effects of ketoconazole in rats.

Irsy G, Koranyi L.

1st Department of Medicine, Postgraduate Medical School, Budapest, Hungary.

The effect of ketoconazole on steroid synthesis was studied in intact (sham-operated) and castrated male and ovariectomized female rats. Rats were given 25 mg/kg ketoconazole twice a day im for 5 days. The influence of ketoconazole was also investigated on hormone release altered by GnRH, estradiol and haloperidol. The following hormones were measured: serum LH, PRL, testosterone, corticosterone, 17-OH-progesterone, estradiol, and dopamine content of the tubero-infundibular area. Ketoconazole treatment resulted in a significant decrease of testerone level (from 7.93 +/- 1.99 to 3.83 +/- 0.94 nmol/l), whereas LH, PRL, corticosterone and 17-OH-progesterone remained unchanged in the male rat. The effect of castration on LH level was reduced by ketoconazole in male (from 590 +/- 35 to 390 +/- 25 micrograms/l) and female rats (from 468 +/- 22 to 346 +/- 39 micrograms/l), but the GnRH-stimulated LH release in castrated and ovariectomized animals was unchanged. The suppressive action of estradiol on LH in ovariectomized rats was enhanced (from 160 +/- 41 to 64.6 +/- 12.9 micrograms/l), and its priming effect on PRL release was diminished by ketoconazole (from 598 +/- 81 to 281 +/- 66 micrograms/l). Ketoconazole failed to modify the tubero-infundibular dopamine content and haloperidol-induced PRL release. It can be assumed that in addition to its inhibitory role of steroid biosynthesis ketoconazole has an influence on central mechanisms underlying LH and PRL release.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2327219&dopt=Abstract ketoconazole Nizoral



Nizoral
The effect of ketoconazole on fertility of male rats.

Waller DP, Martin A, Vickery BH, Zaneveld LJ.

Department of Pharmacodynamics, College of Pharmacy, University of Illinois, Chicago.

The effect of ketoconazole on the fertility of male rats was evaluated. Three days of oral dosing with ketoconazole at 200 mg/kg reduced fertility compared to controls. A complete loss of fertility was observed after doses of 400 mg/kg. There was no change in the testicular weight, epididymal sperm concentration or epididymal weight between the control and treatment groups. Motility was reduced in the high-dose group and forward progression was reduced in both dosing groups compared to control. These data support previous observations in the dog and primate that orally administered ketoconazole alters sperm viability. Although ketoconazole is too toxic for contraceptive application, its derivatives may be useful for this purpose.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2335105&dopt=Abstract ketoconazole Nizoral



Nizoral
[Mycetoma]

[Article in Russian]

Bilusiak DM, Sviridiuk VZ.

Mycetoma is a variety of deep mycoses. The endemic centres are situated in the countries with tropic or subtropic climate. In diagnosis, the important place belongs to microbiological, histological and roentgenological investigations. Surgical treatment supposes the radical removal of a pathological focus in aiming at preservation of the weight-bearing surface of an extremity. In intact skin, the subcutaneous incision of the mycous infiltrate is performed. The extensive soft tissue defects, especially at the region of joints, require primary or secondary autodermoplasty. The medicamentous treatment of fungal mycetomas is ineffective. The positive effect of Ketocanazole (Nizoral) before the operation was noted.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2338778&dopt=Abstract ketoconazole Nizoral



Nizoral
[Determination of biological activity of hydrogel preparations based on ketoconazole and clotrimazole]

[Article in Russian]

Papazova NA, Gorbunova NA, Abramovich RA.

Biological activity of original hydrogel preparations based on ketoconazole and clotrimazole was estimated biologically with the 3-dose variant of the agar-diffusion method. The optimal concentrations of the active substances in the hydrogels were the following: 2% of ketoconazole and 1% for clotrimazole.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15285406&dopt=Abstract ketoconazole Nizoral



Nizoral
In vitro susceptibility of dermatophytes from Munich to griseofulvin, miconazole and ketoconazole.

Korting HC, Rosenkranz S.

Department of Dermatology and Venereology, Ludwig-Maximilians-Universitat, Munich, Germany FR.

Various recent clinical isolates of Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum canis and Epidermophyton floccosum from Munich were subjected to antimicrobial susceptibility testing using the microdilution method. Both azoles miconazole and ketoconazole were found to be more active than griseofulvin. Comparatively high inhibitory concentrations of griseofulvin were especially found with Tr. mentagrophytes. On the whole miconazole turned out to be even somewhat more effective than ketoconazole. Considering the minimum inhibitory concentrations found at least some of the strains tested might not be open to eradication in clinical terms with conventional treatment protocols.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2359418&dopt=Abstract ketoconazole Nizoral



Nizoral
Fluconazole for ketoconazole-resistant oropharyngeal candidiasis in HIV-1 infected patients.

Thorsen S, Mathiesen LR.

Department of Infectious Diseases, University of Copenhagen, Hvidovre Hospital, Denmark.

The efficacy of fluconazole in doses ranging from 50 to 200 mg/day in controlling oropharyngeal candidiasis was retrospectively evaluated in 16 consecutive HIV-1-infected patients. 13 patients received fluconazole due to failure of treatment with ketoconazole, and among these 11 (84%) initially showed complete or partial remission of oropharyngeal candidiasis. 3 (27%) of these subsequently developed failure of treatment within a median observation period of 38 days. No major toxicities were observed. Fluconazole appears promising in the therapy of ketoconazole-resistant candidiasis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2371551&dopt=Abstract ketoconazole Nizoral