Nizoral
The effect of ketoconazole and itraconazole on the filamentous form of Pityrosporum ovale.

Faergemann J, Borgers M.

Department of Dermatology, University of Gothenburg, Sahlgren's Hospital, Sweden.

The effect of ketoconazole and itraconazole on the filamentous form of Pityrosporum ovale in vitro was studied. In a recently developed model, using human stratum corneum in vitro, P. ovale transformed into the filamentous form in 25-30% of the cells. Ketoconazole and itraconazole in concentrations of 0.01, 0.1 and 1 microgram/ml were incubated together with P. ovale cells on human stratum corneum pieces placed on a lipid-enriched culture medium. Both agents effectively blocked the production of hyphae. From the low concentration onwards, the changes consisted of a diminishing transformation into hyphae. With transmission electron microscopy, the interior of many cells was often in an advanced stage of necrosis. Exposure to 1 microgram/ml itraconazole causes a disorganization of the internal organelles in 83% of the cells. This model for the production of hyphae of P. ovale in vitro proved very valuable in screening the activity of antimycotic agents against the filamentous form of this yeast.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1969209&dopt=Abstract ketoconazole Nizoral



Nizoral
Serum binding of ketoconazole in health and disease.

Martinez-Jorda R, Rodriguez-Sasiain JM, Suarez E, Calvo R.

Department of Pharmacology, School of Medicine, Basque Country University, Leioa, Bizkaia, Spain.

The plasma protein binding of ketoconazole, an oral antifungal agent of a weak basic nature, was measured after the addition of the drug (10 micrograms.ml-1) to serum from 35 healthy individuals, ten patients with chronic renal disease and seven patients with hepatic cirrhosis. The percentage of free ketoconazole was markedly increased in patients with chronic renal disease and in patients with hepatic cirrhosis, when it was compared with the group of healthy volunteers (7.33 +/- 0.11 in renal patients; 6.12 +/- 1.43 in hepatic patients compared with 2.93 +/- 0.12 in healthy individuals). The binding ratio of ketoconazole in health and disease was significantly related to plasma albumin concentration, but not to plasma alpha 1-acid glycoprotein (AAG) concentration. Moreover, ketoconazole binds to isolated human serum albumin in a greater proportion but does not bind to isolated AAG indicating that human serum albumin is the major binding protein for this drug in plasma.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2079384&dopt=Abstract ketoconazole Nizoral



Nizoral
Susceptibility of several species of Candida and Torulopsis to fluconazole and ketoconazole.

Mallie M, Montes B, Reynes J, Bastide JM.

Laboratory of Immunology and Parasitology, Faculty of Pharmacy, Montpellier, France.

The authors compared the in vitro antifungal activity of fluconazole, a new triazole antifungal agent, and ketoconazole, an imidazole derivative. The MIC values were determined against 50 strains of Candida albicans, 10 strains of C. guilliermondii, 10 strains of C. krusei, 10 strains of C. parapsilosis, 10 strains of C. pseudotropicalis, 10 strains of C. tropicalis and 15 strains of Torulopsis glabrata. The fungistatic activity was evaluated by the agar dilution method using BHI and casitone media after incubation for 48 h at 28-30 degrees C. Both antifungal agents showed higher activity when tested on casitone medium; however, the G-MIC values for ketoconazole were lower than those for fluconazole.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2100733&dopt=Abstract ketoconazole Nizoral



Nizoral
Skin surface electron microscopy in Pityrosporum folliculitis. The role of follicular occlusion in disease and the response to oral ketoconazole.

Hill MK, Goodfield JD, Rodgers FG, Crowley JL, Saihan EM.

Department of Microbiology, University Hospital, Queen's Medical Centre, Nottingham, England.

The yeast Pityrosporum orbiculare is thought to cause the folliculitis associated with seborrheic eczema. However, a combination of mechanical and microbiological factors may be involved, with follicular occlusion leading to yeast overgrowth and folliculitis. Scanning electron microscopy was used to investigate this hypothesis. Skin biopsy specimens obtained from patients with Pityrosporum folliculitis were examined by scanning electron microscopy before and after oral ketoconazole therapy. Patients with active disease showed occlusion of noninflamed follicles, which resolved after ketoconazole treatment. Follicular occlusion was not present in biopsy specimens obtained from unaffected controls nor was it related to the presence of P orbiculare. These findings suggest that follicular occlusion may be a primary event in the development of this folliculitis, with yeast overgrowth a secondary occurrence. The beneficial effect of ketoconazole in this disease may be due to direct effects on the follicle.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2137322&dopt=Abstract ketoconazole Nizoral



Nizoral
Comparison of fluconazole and ketoconazole in experimental murine blastomycosis.

Stevens DA, Brummer E, McEwen JG, Perlman AM.

Department of Medicine, Santa Clara Valley Medical Center, San Jose, California 95128.

Fluconazole, a new oral triazole antifungal agent, was tested against Blastomyces dermatitidis in vitro and in a murine model (pulmonary challenge) and compared with ketoconazole, an oral imidazole known to be effective against this agent in mice and in humans. Although fluconazole appeared less active than ketoconazole in vitro, in experiments involving 3 weeks of treatment and 2 months of observation, fluconazole was greater than 10 times as potent (mg/kg) in vivo against blastomycosis (prolongation of life). In the model neither drug was curative at the doses and regimens used. A possible explanation for the efficacy of fluconazole in vivo is its favorable pharmacokinetic profile (i.e., prolonged serum concentrations that exceeded the MIC for the pathogen after oral administration). Dosages of 100 mg/(kg.d) were tolerated for 3 weeks without evident toxicity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2139516&dopt=Abstract ketoconazole Nizoral



Nizoral
The in vitro antifungal activity of ketoconazole, zinc pyrithione, and selenium sulfide against Pityrosporum and their efficacy as a shampoo in the treatment of experimental pityrosporosis in guinea pigs.

Van Cutsem J, Van Gerven F, Fransen J, Schrooten P, Janssen PA.

Janssen Research Foundation, Beerse, Belgium.

The fungistatic and fungicidal activity of ketoconazole, zinc pyrithione, and selenium sulfide against Pityrosporum, a yeast thought to play a pathogenic role in seborrheic dermatitis and dandruff, was assessed in Dixon broth for Pityrosporum ovale and Sabouraud broth for Pityrosporum pachydermatis. Ketoconazole inhibited growth at concentrations ranging from 0.001 to 1 micrograms/ml. For zinc pyrithione and selenium sulfide higher concentrations were needed. In a guinea pig model the efficacy of treatment with four shampoos (Nizoral [Jansen], EDS Zinc [Schering], Zinkan [Lederle], and Selsun [Abbott]) was compared. The animals were inoculated for 7 consecutive days on intact skin. The lesions were scored for erythema, folliculitis, and hyperkeratosis 24 hours after the last inoculation and after treatment. Final evaluations were made 13 days after infection (10 days after last shampoo application). Treatment with undiluted and diluted (1:10) shampoos showed consistently superior clinical and mycologic results for Nizoral shampoo. None of the shampoos produced side effects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2142498&dopt=Abstract ketoconazole Nizoral



Nizoral
Topical ketoconazole for infantile seborrhoeic dermatitis.

Taieb A, Legrain V, Palmier C, Lejean S, Six M, Maleville J.

Service de Dermatologie Pediatrique, Hopital des Enfants, Bordeaux, France.

In an open study, 19 infants with a bipolar seborrhoeic rash were treated with ketoconazole 2% in cream once a day and evaluated over 10 days of treatment. At day 10, 78.9% of patients were almost cleared. Percutaneous absorption peaked 1-3 h after topical treatment, and was minimal. No plasma ketoconazole accumulation over the 10-day treatment was detected. Treatment failures corresponded to histologically psoriasiform eruptions and probable atopic dermatitis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2144249&dopt=Abstract ketoconazole Nizoral