Animals ; Hepatocytes ; Ketoconazole/pharmacology* ; Liver/pathology* ; Male ; Mice ; Testis/pathology*

Background: Oral azole drugs are a second-line option for the treatment of pityriasis versicolor but evidence on their efficacy and safety is unclear. Objectives. To determine the efficacy and safety of oral azoles in the treatment of patients with pityriasis Versicolor.

Methods: We searched MEDLINE, CENTRAL, EMBASE, LILACS, and HERDIN, from inception to the period between January to February 2014. We did not restrict the search by language or publication status. We included randomized controlled trials (RCTs) that compared the efficacy of oral azoles with placebo or no treatment, with topical agents, other oral azoles or dosing regimens in the treatment of pityriasis Versicolor, and that measured any of the pre-specified outcomes (mycologic cure, clinical cure, recurrence, duration to cure, time-to-cure, and quality of life). For adverse effects, we also included non-randomized studies (NRS). We used Cochrane methods to select studies, extract data, assess the risk of bias, pool studies, and calculate for treatment effects.

Results: We included 38 RCTs (n=2894) and 56 NRS (n=3452). Overall, there were few pooled studies and evidence was low to moderate quality. Oral azoles were more effective than placebo (mycologic cure, RR 11.34, 95% CI 4.90, 26.28; 3 RCTs, n=131; I2=0%; low quality of evidence) and as effective as topical agents (mycologic cure, RR 1.02, 95% CI 0.86, 1.21; 4 RCTs, n=232; I2=60%; moderate quality of evidence).There were few adverse effects and were mostly minor and transient.

Conclusions: Oral azoles may be more effective than placebo, and are probably as effective as topical agents in the treatment of PV. Triazoles are probably as effective as ketoconazole. Adverse effects were few, mostly minor, and transient.

Ketoconazole ; Itraconazole ; Fluconazole ; Tinea Versicolor ; Pityriasis ; Systematic Review ; Meta-analysis

Breast cancer is currently the most prevalent cancer in women, and its incidence increases every year. Azole antifungal drugs were recently found to have antitumor efficacy in several cancer types. They contain an imidazole (clotrimazole and ketoconazole) or a triazole (fluconazole and itraconazole) ring. Using human breast adenocarcinoma cells (MCF-7 and MDA-MB-231), we evaluated the effects of azole drugs on cell proliferation, apoptosis, cell cycle, migration, and invasion, and investigated the underlying mechanisms. Clotrimazole and ketoconazole inhibited the proliferation of both cell lines while fluconazole and itraconazole did not. In addition, clotrimazole and ketoconazole inhibited the motility of MDA-MB-231 cells and induced G₁-phase arrest in MCF-7 and MDA-MB-231 cells, as determined by cell cycle analysis and immunoblot data. Moreover, Transwell invasion and gelatin zymography assays revealed that clotrimazole and ketoconazole suppressed invasiveness through the inhibition of matrix metalloproteinase 9 in MDA-MB-231 cells, although no significant changes in invasiveness were observed in MCF-7 cells. There were no significant changes in any of the observed parameters with fluconazole or itraconazole treatment in either breast cancer cell line. Taken together, imidazole antifungal drugs showed strong antitumor activity in breast cancer cells through induction of apoptosis and G₁ arrest in both MCF-7 and MDA-MB-231 cells and suppression of invasiveness via matrix metalloproteinase 9 inhibition in MDA-MB-231 cells. Imidazole drugs have well-established pharmacokinetic profiles and known toxicity, which can make these generic drugs strong candidates for repositioning as antitumor therapies.
Adenocarcinoma ; Apoptosis ; Breast Neoplasms* ; Breast* ; Cell Cycle ; Cell Line ; Cell Proliferation* ; Clotrimazole ; Danazol ; Drugs, Generic ; Female ; Fluconazole ; Gelatin ; Humans* ; Incidence ; Itraconazole ; Ketoconazole ; Matrix Metalloproteinase 9 ; MCF-7 Cells

An 8-year-old castrated male Shih Tzu dog (weighing 7.0 kg) presented with anemia and lethargy. Initial diagnosis indicated immune-mediated hemolytic anemia. During therapy, a secondary urinary infection, probably due to the immune suppressive therapy, was diagnosed. Subsequent diagnostic tests, including urinalysis and urine culture, indicated candidal cystitis. Despite ketoconazole therapy for candidal cystitis, the dog died suddenly. A Candida albicans infection was confirmed upon postmortem evaluation. Prolonged immunosuppressive therapy might be the cause of this infection. This is the first case report describing a Candida albicans urinary tract infection accompanied by hemolytic anemia in a dog in Korea.
Anemia ; Anemia, Hemolytic* ; Animals ; Candida albicans* ; Candida* ; Child ; Cystitis ; Diagnosis ; Diagnostic Tests, Routine ; Dogs* ; Humans ; Ketoconazole ; Korea ; Lethargy ; Male ; Urinalysis ; Urinary Tract Infections* ; Urinary Tract*

OBJECTIVE: To identify and assess the available literature in evaluating the efficacy and safety of ketoconazole in preventing postoperative erection among patients who underwent penile or urethral reconstructive surgery.
METHODS: From the period of 1990 to September 2016, the investigators assessed Cochrane Central Register of Controlled Trials, EMBASE, HERDIN, and PubMed for studies evaluating the efficacy and safety of ketoconazole in preventing post operative erection among patients who underwent penile or urethral reconstructive surgery. Review authors selected articles for inclusion, extracted date and and assessed trial quality.
RESULTS: One randomized controlled study and 2 retrospective studies were included in the review. Three studies for a total of 83 patients ages 17-32 comprised the evidence for this review. All trials investigated the efficacy and safety of ketoconazole in the prevention of post operative erection. In both retrospective studies, ketoconazole had significant prevention of erection in however both of these studies were non-RCTs. In the randomized control study by DeCastro et.al.,ketoconazole had no significant difference in the prevention of post operative erection against placebo. Sixteen out of 19 patients (84%) taking ketoconazole had episodes of erection and 15 out of 18 patients in the placebo group (83%) had episodes of erection. Common side effects include nausea (9-21%) and elevated liver enzymes (0-5.3%). Other reported adverse events include feet swelling,pruritus,frequent urination and headache. Present in only 1 out of the 31 patients (3.2%) in the study of DeCastro. All these adverse events were not statistically significant.
CONCLUSION: This review demonstrated that the use of Ketoconazole in the prevention of postoperative erection remains inconclusive. Further prospective randomized controlled trials with testosterone assay will help determine the appropriate dose and its efficacy in the prevention of postoperative erections. Ketoconazole is relatively safe if target testosterone levels are achieved using the 400mg/tab TID dosing.

Human ; Male ; Female ; Aged ; Middle Aged ; Adult ; Adolescent ; Headache ; Ketoconazole ; Liver ; Nausea ; Penile Erection ; Penis ; Pruritus ; Reconstructive Surgical Procedures ; Testosterone ; Urethra ; Urination

Sporotrichosis is a chronic cutaneous fungal infection caused by Sporothrix (S.) schenckii complex. Fixed cutaneous sporotrichosis is one of the three subtype of sprotrichosis and accounts for 20% of total sporotrichosis cases. However, the incidence of total sporotrichosis cases is decreasing recently due to improvement of personal hygiene and industrialization. A 60-year-old woman presented to the hospital with multiple erythematous papules and ulcers on left cheek for 5 months. Histopathologic examination revealed chronic granulomatous inflammation and immunohistochemical staining was positive for GMS and PAS stain. The fungal culture on Sabouraud dextrose agar showed grayish dark brown colonies and the sequences of ribosomal DNA internal transcribed spacer region of clinical sample was 100% similarity with S. globosa. The patient was treated with oral itraconazole 200 mg daily and topical ketoconazole cream for 3 months. At that time after this treatment, skin lesion was almost cured and recurrence is not observed to date.
Agar ; Cheek ; DNA, Ribosomal ; Female ; Glucose ; Humans ; Hygiene ; Incidence ; Inflammation ; Itraconazole ; Ketoconazole ; Middle Aged ; Recurrence ; Skin ; Sporothrix* ; Sporotrichosis* ; Ulcer

OBJECTIVE: Midazolam is mainly metabolized by cytochrome P450 (CYP) 3A. Inhibition or induction of CYP3A can affect the pharmacological activity of midazolam. The aims of this study were to develop a population pharmacokinetic (PK) model and evaluate the effect of CYP3A-mediated interactions among ketoconazole, rifampicin, and midazolam. METHODS: Three-treatment, three-period, crossover study was conducted in 24 healthy male subjects. Each subject received 1 mg midazolam (control), 1 mg midazolam after pretreatment with 400 mg ketoconazole once daily for 4 days (CYP3A inhibition phase), and 2.5 mg midazolam after pretreatment with 600 mg rifampicin once daily for 10 days (CYP3A induction phase). The population PK analysis was performed using a nonlinear mixed effect model (NONMEM® 7.2) based on plasma midazolam concentrations. The PK model was developed, and the first-order conditional estimation with interaction was applied for the model run. A three-compartment model with first-order elimination described the PK. The influence of ketoconazole and rifampicin, CYP3A5 genotype, and demographic characteristics on PK parameters was examined. Goodness-of-fit (GOF) diagnostics and visual predictive checks, as well as bootstrap were used to evaluate the adequacy of the model fit and predictions. RESULTS: Twenty-four subjects contributed to 900 midazolam concentrations. The final parameter estimates (% relative standard error, RSE) were as follows; clearance (CL), 31.8 L/h (6.0%); inter-compartmental clearance (Q) 2, 36.4 L/h (9.7%); Q3, 7.37 L/h (12.0%), volume of distribution (V) 1, 70.7 L (3.6%), V2, 32.9 L (8.8%); and V3, 44.4 L (6.7%). The midazolam CL decreased and increased to 32.5 and 199.9% in the inhibition and induction phases, respectively, compared to that in control phase. CONCLUSION: A PK model for midazolam co-treatment with ketoconazole and rifampicin was developed using data of healthy volunteers, and the subject's CYP3A status influenced the midazolam PK parameters. Therefore, a population PK model with enzyme-mediated drug interactions may be useful for quantitatively predicting PK alterations.
Cross-Over Studies ; Cytochrome P-450 CYP3A ; Cytochrome P-450 Enzyme System* ; Cytochromes* ; Drug Interactions ; Genotype ; Healthy Volunteers ; Humans ; Ketoconazole ; Male ; Midazolam* ; Pharmacokinetics* ; Plasma ; Rifampin

Mycetoma is a chronic, debilitating, granulomatous disease affecting the subcutaneous tissue, fascia, muscle, bone and adjacent organs characterized by triad of tumefaction, draining sinus, and grains. The ten-year incidence in our institution from 2000 to 2010 is 3 out of 81,015 cases. We present a 33-year-old man with a nine-year history of painless nodules and draining sinuses on the left foot which were unresponsive to oral antibiotics and topical antifungals. Biopsy of a nodule was consistent with mycetoma. Fungal culture revealed Madurella mycetomatis growth confirming eumycetoma. X-ray of the left foot showed poorly marginated lucencies on the calcaneus and navicular bones. Ultrasound revealed mixed hyperreflective echoes and multiple small cavities. We diagnosed the patient with Stage III eumycetoma based on the radiographic classification of bone involvement and prescribed oral ketoconazole 400 mg daily for nine months achieving 50-60% decrease in lesion size. Surgical debulking was done and ketoconazole was continued at the same dose for another nine months. There was good granulation tissue formation and no appearance of new lesions after surgery.

Human ; Adult ; Anti-bacterial Agents ; Calcaneus ; Cytoreduction Surgical Procedures ; Fascia ; Foot ; Granulation Tissue ; Ketoconazole ; Madurella ; Mycetoma ; Subcutaneous Tissue ; Ultrasonography

Small cell lung cancer (SCLC), which originated from neuroendocrine tissue, can develop into paraneoplastic endocrine syndromes, such as Cushing syndrome, because of an inappropriate secretion of ectopic adrenocorticotropic hormone (ACTH). This paraneoplastic syndrome is known to be a poor prognostic factor in SCLC. The reason for poor survival may be because of a higher risk of infection associated with hypercortisolemia. Therefore, early detection and appropriate treatment for this syndrome is necessary. But the diagnosis is challenging and the source of ACTH production can be difficult to identify. We report a 69-year-old male patient who had severe hypokalemia, metabolic alkalosis, and hypertension as manifestations of an ACTH-secreting small cell carcinoma of the lung. He was treated with ketoconazole and spironolactone to control the ACTH dependent Cushing syndrome. He survived for 15 months after chemotherapy, which is unusual considering the poor outcome of the ectopic ATH syndrome associated with SCLC.
ACTH Syndrome, Ectopic ; Adrenocorticotropic Hormone* ; Aged ; Alkalosis ; Carcinoma, Small Cell ; Cushing Syndrome ; Diagnosis ; Drug Therapy ; Humans ; Hypertension ; Hypokalemia ; Ketoconazole ; Lung ; Male ; Paraneoplastic Endocrine Syndromes ; Paraneoplastic Syndromes ; Small Cell Lung Carcinoma* ; Spironolactone

Trichophyton (T.) tonsurans is a common anthropophilic species, which causes tinea capitis and tinea corporis particularily in Europe and America, but has not been prevalent in Korea. One case with mycoses infection of the scalp and the other with tinea corporis due to T. tonsurans were observed in Korean general population. We confirmed T. tonsurans infection on the basis of the direct microscopic examination and culture from scales and infected hairs of skin lesions. Systemic itraconazole and terbinafine therapy with topical ketoconazole cream led to clinical and mycological recovery in our cases. Infection of T. tonsurans appears to have spread gradually among the general population in Korea. Therefore, athletic and medical associations should make constant observation and take close consideration about T. tonsurans infection.
Americas ; Europe ; Hair ; Humans ; Itraconazole ; Ketoconazole ; Korea ; Mycoses ; Scalp ; Skin ; Sports ; Tinea ; Tinea Capitis ; Trichophyton* ; Weights and Measures