Utilization of the chronic atrioventricular block cynomolgus monkey as an in vivo model to evaluate drug interaction-associated torsade de pointes.

It has been difficult to experimentally reproduce synergistic effects of ketoconazole on terfenadine-induced torsade de pointes. We assessed proarrhythmic effects of terfenadine (30 mg/kg, p.o.) with/without ketoconazole (100 mg/kg, p.o.) pretreatment using the chronic atrioventricular block cynomolgus monkeys with repeated-measured design (n = 4). Terfenadine with ketoconazole pretreatment repeatedly induced non-sustained torsade de pointes in each animal, although terfenadine alone did not induce it at all. Thus, the chronic atrioventricular block cynomolgus monkeys can be used for studying drug interaction-associated torsade de pointes, providing a non-clinical strategy to circumvent untoward drug interactions in patients specially under polypharmacy.

Adapalene gel 0.1% vs ketoconazole cream 2% and their combination in treatment of pityriasis versicolor: A randomized clinical study.

Pityriasis versicolor (PV) is a chronic superficial fungal infection. Management using azole drugs leads to drug resistance. The present study aimed to compare the clinical outcome of 0.1% adapalene gel vs 2% ketoconazole cream and their combination in PV. This randomized double-blinded study was conducted on 90 PV patients divided into three equal groups. GI was treated with topical ketoconazole 2% cream twice daily and placebo, GII was treated with topical 0.1% adapalene gel twice daily and placebo and GIII was treated with topical combination of 0.1% adapalene gel (at night) and ketoconazole 2% cream (in the morning). All patients received medications for 4 weeks. Evaluation was done at 2 and 4 weeks and included clinical assessment, laboratory assessment, and patient satisfaction. We found that after 4 weeks of treatment, all groups showed significant improvement. There was better response in GIII in terms of lower rate of positive potassium hydroxide staining, higher rate of significantly improved cases and higher rate of well-satisfied patients. However, the difference fell short of statistical significance. We concluded that a combination of adapalene gel and ketoconazole cream is very effective in treatment of PV with no or mild side effects.

Enhanced activation of human NK cells by drug-exposed hepatocytes.

Drug-induced liver injury (DILI) represents one of the major causes why drugs have to be withdrawn from the market. In this study, we describe a new interaction between drug-exposed hepatocytes and natural killer (NK) cells. In a previous genome-wide expression analysis of primary human hepatocytes that had been exposed to clinically relevant concentrations of 148 drugs, we found that several activating ligands for NK cell receptors were regulated by various drugs (e.g., valproic acid, ketoconazole, promethazine, isoniazid). Especially expression of the activating NKG2D ligands (MICA, MICB and ULBPs) and the NKp30 ligand B7-H6 were upregulated in primary human hepatocytes upon exposure to many different drugs. Using the human hepatocyte cell lines Huh7 and HepG2, we confirmed that protein levels of activating NK cell ligands were elevated after drug exposure. Hepatocyte cell lines or primary human hepatocytes co-cultivated with NK cells caused enhanced NK cell activation after pretreatment with drugs at in vivo relevant concentrations compared to solvent controls. Enhanced NK cell activation was evident by increased cytotoxicity against hepatocytes and interferon (IFN)-γ production. NK cell activation could be blocked by specific antibodies against activating NK cell receptors. These data support the hypothesis that NK cells can modulate drug-induced liver injury by direct interaction with hepatocytes resulting in cytotoxicity and IFN-γ production.

The myringoplasty of the perforation with otomycosis.

In consideration of the American Journal of Otolaryngology's reviewing and editing my submission, the author(s) undersigned transfers, assigns and otherwise conveys all copyright ownership to Elsevier Inc. in the event that such work is published in the American Journal of Otolaryngology.

Changes in Bile Acid Concentrations after Administration of Ketoconazole or Rifampicin to Chimeric Mice with Humanized Liver.

Drug-induced liver injury (DILI) is a common side effect of several medications and is considered a major factor responsible for the discontinuation of drugs during their development. Cholestasis is a DILI that results from impairment of bile acid transporters, such as the bile salt export pump (BSEP), leading to accumulation of bile acids. Both in vitro and in vivo studies are required to predict the risk of drug-induced cholestasis. In the present study, we used chimeric mice with humanized liver as a model to study drug-induced cholestasis. Administration of a single dose of ketoconazole or rifampicin, known to potentially cause cholestasis by inhibiting BSEP, did not result in elevated levels of alkaline phosphatase (ALP), which are known hepatic biomarkers. The concentration of taurodeoxycholic acid increased in the liver after ketoconazole administration, whereas rifampicin resulted in increased tauromuricholic acid and taurocholic acid (TCA) levels in the liver and plasma. Furthermore, rifampicin resulted in an increase in the uniform distribution of a compound with m/z 514.3, presumed as TCA through imaging mass spectrometry. The mRNA levels of bile acid-related genes were also altered after treatment with ketoconazole or rifampicin. We believe these observations to be a part of a feedback mechanism to decrease bile acid concentrations. The changes in bile acid concentrations results may reflect the initial responses of the human body to cholestasis. Furthermore, these findings may contribute to the screening of drug candidates, thereby avoiding drug-induced cholestasis during clinical trials and drug development.

Ketoconazole plus Lenalidomide in patients with Castration-Resistant Prostate Cancer (CRPC): results of an open-label phase II study.

Introduction Ketoconazole is CYP-17 inhibitor with demonstrated activity in men with castration-resistant prostate cancer (CRPC). Lenalidomide is an antiangiogenic and immunomodulatory agent with broad antitumor activity. We hypothesized that the modulation of the cellular immune response to apoptosis caused by ketoconazole may be increased with the addition of lenalidomide. Methods This is an open-label, non-randomized, single-arm phase II study evaluating the efficacy and safety of the combination of ketoconazole and lenalidomide in patients with CRPC. Treatment schema included standard ketoconazole 400 mg orally three times daily plus hydrocortisone orally (20 mg in the morning and 10 mg at night) in combination with lenalidomide 25 mg orally daily for 21 days in a 28-day cycle and aspirin 75 mg daily. The primary endpoint of this study was response (either by ≥ 50% PSA decline or objective disease assessed by RECIST v1.0). Exploratory endpoints included changes in T cell, dendritic cell (DC) marker counts, and their correlation with PSA response to treatment. Results A total of 34 CRPC patients, median age 69 years, 76% ECOG 0 and 76% with metastases participated in the study. Patients received a median of 2 cycles (range 1-35); nine patients (26%) received >10 cycles of treatment. PSA responses were observed in 17 patients (50%) with 11 patients (32%) achieving a PSA decline of >90%. Among the 9 patients with measurable disease, 2 patients (22%) had PR and 2 other (22%) had SD as best response. Median time to failure (TTF) was 2.7 months (range 0.2-32.8); and 8 patients were treated for ≥ 15 months. Most common adverse events included fatigue (76%), skin reactions (62%), lymphopenia (44%) and anemia (44%). One possible treatment-related death was noted. For 16 patients with available serial correlative data, there was a significant increase in the dendritic cells subsets BDCA-1 (+146.7, -20.1 to +501.1%, p = 0.018) and BDCA-3 (39.8%, -100 to 282.6%, p = 0.001) after 8 weeks of treatment. No association between immune cell counts and PSA response at 8 weeks was observed. Conclusion The combination of ketoconazole and lenalidomide was well tolerated but did not meet the primary endpoint of response, despite durable responses were observed in a selected group of patients. Although ketoconazole has now been replaced with more active novel agents, the combination of novel CYP-17 inhibitors with agents capable of modulating the immune system warrants further prospective investigation. NCT00460031.

Drug interaction at hERG channel: In vitro assessment of the electrophysiological consequences of drug combinations and comparison against theoretical models.

Drugs carry a proarrhythmic risk, which gets even greater when they are used in combination. In vitro assessment of the proarrhythmic potential of drugs is limited to one compound and thus neglects the potential of drug-drug interactions, including those involving active metabolites. Here we present the results of an in vitro study of potential drug-drug interactions at the level of the hERG channel for the combination of up to three compounds: loratadine, desloratadine and ketoconazole. Experiments were performed at room temperature on an automated patch-clamp device CytoPatch 2, with the use of heterogeneously, stably transfected HEK cells. Single drugs, pairs and triplets were used. The results provided as the inhibition of the IKr current for pairs were compared against the calculated theoretical interaction. Models applied to calculate the combined effect of inhibitory actions of simultaneously given drugs include: (1) simple additive model with a maximal inhibition limit of 1 (all channels blocked in 100%); (2) Bliss independence; and (3) Loewe additivity. The observed IC50 values for loratadine, desloratadine and ketoconazole were 5.15, 1.95 and 0.74 µm respectively. For the combination of drugs tested in pairs, the effect was concentration dependent. In lower concentrations, the synergistic effect was observed, while for the highest tested concentrations it was subadditive. To triple the effect, it was subadditive regardless of concentrations. The square root of sum of squares of differences between the observed and predicted total inhibition was calculated to assess the theoretical interaction models. For most of the drugs, the allotopic model offered the best fit.

The myrtus communis L. solution versus ketoconazole shampoo in treatment of dandruff: A double blinded randomized clinical trial.

OBJECTIVE: To evaluate the efficacy and safety of myrtus communis L. solution in the treatment of dandruff and to compare it with ketoconazole. METHODS: This double-blind randomised clinical trial was conducted at Shiraz University of Medical Sciences, Shiraz, Iran, from December 2015 to August 2016, and comprised patients with dandruff aged 18-60 years visiting the dermatology out-patient clinic. The subjects were randomised into two equal groups. The treatment group received myrtus communis L. solution and a placebo shampoo, while the control group received ketoconazole shampoo and a placebo solution. The total duration of the study for each subject was one month and subjects in both groups used their respective interventions 8 times during that period. The parameters studied were pruritus, erythema, severity of scaling, and the extent of scalp involvement. All subjects underwent scalp scaling tests at the beginning, after 10 days and at the end of the 30th day. SPSS 21 was used for data analysis. RESULTS: Of the 90 individuals, there were 45(50%) in each of the two groups. However, 74(82%) subjects completed the third visit and, of them, there were 37(50%) in each group. Both groups showed significant improvement in all outcome measures (p<0.001). There were no significant differences between the groups in terms of efficacy, satisfaction rate and side effects (p>0.05 for each outcome). CONCLUSIONS: Myrtus solution was found to be effective in the treatment of dandruff.

Effect of Incorporation of Antifungal Agents on the Ultimate Tensile Strength of Temporary Soft Denture Liners.

PURPOSE: To investigate the ultimate tensile strength of temporary soft denture liners modified by minimum inhibitory concentrations (MICs) of antifungal agents for Candida albicans biofilm (SC5314) determined in previous microbiological research. MATERIALS AND METHODS: Dumbbell-shaped specimens (n = 7) with a central cross-sectional area of 6 × 3 × 33 mm were produced by Softone and Trusoft, without (control) or with incorporation of drugs in powder form at MICs for C. albicans biofilm (per g of material powder): nystatin (0.032 g), chlorhexidine diacetate (0.064 g), ketoconazole (0.128 g), miconazole (0.256 g), and itraconazole (0.256 g). After plasticization, specimens were immersed in distilled water at 37°C for 24 hours, 7 or 14 days, and then tested in tension in a universal testing machine at 40 mm/min. Data of tensile strength (MPa) and elongation percentage (%) were submitted to 3-way ANOVA and Tukey's test (α = 0.05). RESULTS: At the end of 14 days, the tensile strength for both materials was significantly lower in the groups modified by miconazole and itraconazole compared to the other groups (p < 0.0001), which showed no significant difference between them (p > 0.05). After 7 and 14 days in water, miconazole and itraconazole added into both materials resulted in significantly lower elongation percentages compared to the other antifungal agents and control (p < 0.0001), which were similar to each other (p > 0.05). CONCLUSIONS: The addition of the nystatin, chlorhexidine, and ketoconazole at MICs for C. albicans biofilm resulted in no harmful effects on the tensile strength and elongation percentage of the temporary soft denture liner materials up to 14 days.

Characterization of chemical-induced sterile inflammation in vitro: application of the model compound ketoconazole in a human hepatic co-culture system.

Liver injury as a result of a sterile inflammation is closely linked to the activation of immune cells, including macrophages, by damaged hepatocytes. This interaction between immune cells and hepatocytes is as yet not considered in any of the in vitro test systems applied during the generation of new drugs. Here, we established and characterized a novel in vitro co-culture model with two human cell lines, HepG2 and differentiated THP-1. Ketoconazole, an antifungal drug known for its hepatotoxicity, was used as a model compound in the testing of the co-culture. Single cultures of HepG2 and THP-1 cells were studied as controls. Different metabolism patterns of ketoconazole were observed for the single and co-culture incubations as well as for the different cell types. The main metabolite N-deacetyl ketoconazole was found in cell pellets, but not in supernatants of cell cultures. Global proteome analysis showed that the NRF2-mediated stress response and the CXCL8 (IL-8) pathway were induced by ketoconazole treatment under co-culture conditions. The upregulation and ketoconazole-induced secretion of several pro-inflammatory cytokines, including CXCL8, TNF-α and CCL3, was observed in the co-culture system only, but not in single cell cultures. Taking together, we provide evidence that the co-culture model applied might be suitable to serve as tool for the prediction of chemical-induced sterile inflammation in liver tissue in vivo.

Pediatric Onychomycosis: The Emerging Role of Topical Therapy.

Fungal infection of the nails is an increasingly recognized disease in infants and children. However, it can be difficult to distinguish clinically from other nail dystrophies. In addition, many mistakenly believe that onychomycosis does not occur in childhood. Under-recognition of this infectious disorder therefore occurs. Although many consider "nail fungus" a trivial cosmetic concern, it can lead to discomfort, risk of secondary infection, and a more significant health threat in immunocompromised or diabetic individuals. It should always be considered in the differential diagnosis of nail plate disorders in children as it is one of the more common causes.

Here we review the latest data on prevalence of the disease, reasons for its relatively low incidence compared with adults, and important predisposing factors. It is important to confirm the clinical diagnosis of onychomycosis in children, and affected individuals should be examined for concomitant tinea pedis. As familial disease often occurs, it is important to check parents and siblings as well for onychomycosis and tinea pedis.

Treatment of onychomycosis is challenging, and recurrence appears to be more common in children than in adults. Prolonged systemic antifungal therapy is commonly required. However, pediatric practitioners and parents alike hesitate when asked to treat young children with a systemic drug that requires laboratory monitoring and can have systemic toxicities. Due to their thinner, faster-growing nails, children are theoretically more likely to respond to topical monotherapy than adults, and therefore good candidates for topical antifungal therapy.

The clinical data on the use of topical antifungals in pediatric onychomycosis is scarce. We review data that exist from case reports and small clinical trials. New topical antifungals are now available that afford better nail penetration and additional delivery routes to the site of infection. Pediatric trials are now on-going, and should clarify the usefulness of these agents in children.

Putative contact ketoconazole shampoo-triggered pemphigus foliaceus in a dog.

A 10-year-old spayed female cocker spaniel dog was referred for an evaluation of acute-onset generalized pustular cutaneous lesions following application of ketoconazole shampoo. Cytologic and histopathologic examinations of the lesions revealed intra-epidermal pustules with predominantly neutrophils and acantholytic cells. This is the first description of putative contact ketoconazole shampoo-triggered pemphigus foliaceus in a dog.

Pemphigus foliaceus causé par le contact putatif avec un shampoing au kétoconazole chez un chien. Une chienne Cocker spaniel stérilisée âgée de 10 ans a été recommandée pour l'évaluation de l'apparition de lésions cutanées pustulaires générales après l'application d'un shampoing au kétoconazole. Les examens cytologiques et histopathologiques des lésions ont révélé des pustules intra-épidermiques composées surtout de neutrophiles et de cellules acantholysées. Il s'agit de la première description de pemphigus foliaceus causé par le contact putatif avec un shampoing au kétoconazole chez un chien.(Traduit par Isabelle Vallières).

The Investigational Drug VT-1129 Is a Highly Potent Inhibitor of Cryptococcus Species CYP51 but Only Weakly Inhibits the Human Enzyme.

Cryptococcosis is a life-threatening disease often associated with HIV infection. Three Cryptococcus species CYP51 enzymes were purified and catalyzed the 14α-demethylation of lanosterol, eburicol, and obtusifoliol. The investigational agent VT-1129 bound tightly to all three CYP51 proteins (dissociation constant [Kd] range, 14 to 25 nM) with affinities similar to those of fluconazole, voriconazole, itraconazole, clotrimazole, and ketoconazole (Kd range, 4 to 52 nM), whereas VT-1129 bound weakly to human CYP51 (Kd, 4.53 µM). VT-1129 was as effective as conventional triazole antifungal drugs at inhibiting cryptococcal CYP51 activity (50% inhibitory concentration [IC50] range, 0.14 to 0.20 µM), while it only weakly inhibited human CYP51 activity (IC50, ∼600 µM). Furthermore, VT-1129 weakly inhibited human CYP2C9, CYP2C19, and CYP3A4, suggesting a low drug-drug interaction potential. Finally, the cellular mode of action for VT-1129 was confirmed to be CYP51 inhibition, resulting in the depletion of ergosterol and ergosta-7-enol and the accumulation of eburicol, obtusifolione, and lanosterol/obtusifoliol in the cell membranes.

Ritonavir is the best alternative to ketoconazole as an index inhibitor of cytochrome P450-3A in drug-drug interaction studies.

AIMS: The regulatory prohibition of ketoconazole as a CYP3A index inhibitor in drug-drug interaction (DDI) studies has compelled consideration of alternative inhibitors. METHODS: The biomedical literature was searched to identify DDI studies in which oral midazolam (MDZ) was the victim, and the inhibitory perpetrator was either ketoconazole, itraconazole, clarithromycin, or ritonavir. The ratios (RAUC ) of total area under the curve (AUC) for MDZ with inhibitor divided by MDZ AUC in the control condition were aggregated across individual studies for each inhibitor. RESULTS: Mean (± SE) RAUC values were: ketoconazole (15 studies, 131 subjects), 11.5 (±1.2); itraconazole (five studies, 48 subjects), 7.3 (±1.0); clarithromycin (five studies, 73 subjects), 6.5 (±10.9); and ritonavir (13 studies, 159 subjects), 14.5 (±2.0). Differences among inhibitors were significant (F = 5.31, P < 0.005). RAUC values were not significantly related to inhibitor dosage or to duration of inhibitor pre-exposure prior to administration of MDZ. CONCLUSIONS: Ritonavir produces CYP3A inhibition equivalent to or greater than ketoconazole, and is the best index CYP3A inhibitor alternative to ketoconazole. Cobicistat closely resembles ritonavir in structure and function, and can also be considered. Itraconazole and clarithromycin are not suitable alternatives since they do not produce inhibition comparable with ketoconazole or ritonavir, and have other significant disadvantages as well.

Ketoconazole-induced Sweet syndrome: a new association.

Sweet syndrome (SS) is an acute febrile neutrophilic dermatosis that can be associated with malignancy and medications. A 60-year-old man presented with erythematous, edematous, and ulcerated plaques in the extensor surface of the upper extremities, after a ketoconazole course due to pityrosporum folliculitis. Skin biopsy showed a dense dermal neutrophilic infiltrate, associated with marked papillary dermal edema. Blood count showed leukocytosis and neutrophilia. Skin lesions resolved spontaneously with discoloration after 2 weeks of discontinuation of ketoconazole. Although most cases of drug-induced SS are associated with granulocyte colony-stimulating factor, other medications need to be considered. This is the first reported case of ketoconazole-induced SS despite its widespread use.

Chloramphenicol significantly affects the pharmacokinetics of oral methadone in Greyhound dogs.

OBJECTIVE: To assess the effects of cytochrome P450 (CYP) inhibitors (ketoconazole, chloramphenicol, trimethoprim, fluoxetine, cimetidine and medetomidine) in various combinations on the pharmacokinetics of oral methadone in Greyhound dogs to determine the specific effects of the different inhibitors and if a clinically relevant interaction occurs. STUDY DESIGN: Non-randomized, sequential design. ANIMALS: Six healthy Greyhound dogs (three male, three female). METHODS: Canine CYP inhibitors (ketoconazole, chloramphenicol, trimethoprim, fluoxetine, cimetidine and medetomidine) were administered in varying combinations prior to the administration of oral methadone. Plasma was obtained from each dog to enable the determination of methadone and CYP inhibitor drug concentrations using liquid chromatography with either mass spectrometry or ultraviolet detection. RESULTS: Significant increases in the area under the curve (AUC) and maximum plasma concentrations (CMAX ) of methadone occurred in all groups administered chloramphenicol. The AUC (6 hours ng mL(-1)) and CMAX (6 ng mL(-1)) of methadone significantly increased to 541 hours ng mL(-1) and 47.8 ng mL(-1), respectively, when methadone was administered with chloramphenicol as a sole inhibitor. There were no significant effects of CYP inhibitors other than chloramphenicol on methadone pharmacokinetics, which suggests that chloramphenicol was primarily responsible for the pharmacokinetic interaction. CONCLUSIONS AND CLINICAL RELEVANCE: This study demonstrated significant effects of chloramphenicol on the pharmacokinetics of oral methadone. Further studies should investigate the effects of chloramphenicol on methadone pharmacokinetics in multiple dog breeds and examine whether oral methadone would be an effective analgesic in dogs. In addition, the safety of chloramphenicol and its effects on the pharmacokinetics of parenteral methadone warrant assessment.

[Cutaneous Malassezia infections and Malassezia associated dermatoses: An update]. / Kutane Malassezia-Infektionen und Malassezia-assoziierte Dermatosen : Ein Update.

The lipophilic yeast fungus Malassezia (M.) spp. is the only fungal genus or species which is part of the physiological human microbiome. Today, at least 14 different Malassezia species are known; most of them can only be identified using molecular biological techniques. As a facultative pathogenic microorganism, Malassezia represents the causative agent both of superficial cutaneous infections and of blood stream infections. Pityriasis versicolor is the probably most frequent infection caused by Malassezia. Less common, Malassezia folliculitis occurs. There is only an episodic report on Malassezia-induced onychomycosis. Seborrhoeic dermatitis represents a Malassezia-associated inflammatory dermatosis. In addition, Malassezia allergenes should be considered as the trigger of "Head-Neck"-type atopic dermatitis. Ketoconazole possesses the strongest in vitro activity against Malassezia, and represents the treatment of choice for topical therapy of pityriasis versicolor. Alternatives include other azole antifungals but also the allylamine terbinafine and the hydroxypyridone antifungal agent ciclopirox olamine. "Antiseborrhoeic" agents, e.g. zinc pyrithione, selenium disulfide, and salicylic acid, are also effective in pityriasis versicolor. The drug of choice for oral treatment of pityriasis versicolor is itraconazole; an effective alternative represents fluconazole. Seborrhoeic dermatitis is best treated with topical medication, including topical corticosteroids and antifungal agents like ketoconazole or sertaconazole. Calcineurin inhibitors, e.g. pimecrolimus and tacrolimus, are reliable in seborrhoeic dermatitis, however are used off-label.

Can pityriasis versicolor be treated with 2% ketoconazole foam?

BACKGROUND: Pityriasis (tinea) versicolor is a superficial fungal infection of the stratum corneum caused by Malassezia species. The diagnosis is made clinically by its classic appearance of round or oval macules with fine scale that may be hyperpigmented or hypopigmented. Diagnosis may also be confirmed with microscopic evaluation of skin scrapings that reveal both short, stubby hyphae, and spores under KOH preparation. Ketoconazole is an important treatment of pityriasis versicolor but is primarily used in cream formulas. A foam vehicle has been shown to improve drug absorption through the stratum corneum and distribution in the skin. This study has assessed the safety and efficacy of ketoconazole 2% foam in treatment of pityriasis versicolor. METHODS: Ketoconazole 2% foam was evaluated in a single-center, open-label, one-arm pilot study which enrolled eleven subjects to gain 10 evaluable subjects aged 21 years and older with a clinical diagnosis of tinea versicolor and positive KOH using calcofluor. The subjects came for 4 scheduled visits (baseline, week 1, week 2, and week 4) and were instructed to apply ketoconazole 2% foam to all affected areas twice daily for 2 weeks. At each visit, mycological and clinical assessment of a target area was done, along with static global assessment and body surface area estimation of the disease in each subject. Patient questionnaires were given at baseline and at week 2 to rate pruritus and satisfaction with the foam. RESULTS: At the week 2 visit, following the treatment period, three out of ten evaluable subjects had negative skin samples prepared with KOH/calcifluor. Of these three, one subject later showed recurrence of fungal elements consistent with tinea versicolor at the week 4 follow-up visit. The other negative subjects remained negative and four additional subjects tested negative at week 4. Three subjects with positive samples at week 4 had only yeast forms without hyphae present. Investigator ratings of the target area were averaged for each clinical feature and demonstrated improvement in scale, hyper- or hypopigmentation, erythema, and induration throughout the study. Average pruritus score increased slightly 1 week after the baseline visit, but then improved steadily over the remaining visits. The investigator's static global assessment rating showed improvement from mild to moderate disease at baseline to minimal or no disease at week 4 in 7 subjects. The remaining subjects showed neither improvement nor progression of the disease throughout the study. One out of the eleven subjects enrolled did not complete the study. One subject noted mild skin burning sensation after application of medicine. Post-treatment patient questionnaires indicated overall satisfaction with the foam vehicle. LIMITATIONS: This was a single-arm, open-label, noncomparative trial. CONCLUSION: Ketoconazole 2% foam improved overall clinical assessment and microscopic evidence of pityriasis versicolor in all subjects with favorable patient feedback regarding the novel foam vehicle.