Successful treatment of herpes labialis with topical acyclovir.

A double blind, placebo controlled trial of 5% acyclovir cream, applied topically five times a day for five days, was carried out in 49 patients with recurrent herpes labialis. These patients had a total of 74 episodes, 34 of which were treated with the 5% acyclovir cream and 40 with matching placebo. First episodes and all episodes treated with acyclovir cream had significantly shorter times to formation of ulcer or crust and to complete healing (p less than 0.05 for all variables). The duration of all symptoms and proportion of patients developing itching was also reduced by acyclovir cream in first episodes, though the difference was not significant. When the patient started treatment early in the course of a first episode acyclovir cream significantly reduced the percentage of lesions progressing beyond the papular stage (p less than 0.05). Acyclovir cream is well tolerated and effective for the treatment of recurrent herpes labialis.     

Oral acyclovir in acute herpes zoster.

Oral acyclovir at a dose of 800 mg five times daily for seven days was compared with placebo in a randomised double blind trial conducted at three centres in the United Kingdom. The study group comprised 205 elderly immune competent patients suffering from herpes zoster who were entered within 72 hours of the onset of rash. Acyclovir significantly reduced the times to arrest of new lesion formation (p = 0.005), loss of vesicles (p less than 0.001), and full crusting (p = 0.02) in those patients entered within 48 hours of the onset of rash. In addition, there was a significant reduction in pain during treatment with acyclovir as compared with placebo (p = 0.008). Of the patients with severe pain on entry, 40% (10/25) of those treated with acyclovir had no or only mild pain at the end of treatment, whereas in the placebo group all had residual moderate or severe pain (p less than 0.001). No clinically important adverse effects of acyclovir were reported. Oral acyclovir may modify acute herpes zoster and reduce pain.     

A comparative multi-centre study of the efficacy of propolis, acyclovir and placebo in the treatment of genital herpes (HSV).

Ninety men and women with recurrent genital HSV type 2 participated in a randomized, single-blind, masked investigator, controlled multi-centre study comparing the efficacy of ointment of Canadian propolis containing natural flavonoids with ointments of acyclovir and placebo (vehicle) on healing ability and capacity to remedy symptoms. Thirty individuals were randomized to each group. Treatment was intended to start in the blister phase. All participants had HSV type 2 isolated, confirmed by serum immunoglobulin levels. The participants were examined on the 3rd, 7th and 10th days of treatment by gynaecologists, dermatovenerologists or urologists at seven different medical centres. Apart from clinical symptoms the number and size of the herpetic lesions were noted. At each examination the lesions were classified into four stages: vesicular, ulcerated, crusted and healed. The study ointments were applied to affected areas four times daily. In women with vaginal or cervical lesions a tampon with the appropriate ointment was inserted four times daily for 10 days. Endpoint variables were healing time and time until loss of symptoms. RESULTS: On Day 10, 24 out of 30 individuals in the propolis group had healed. In the acyclovir group 14 out of 30 and in the placebo group 12 out of 30 had healed. (p = 0.0015). The healing process appeared to be faster in the propolis group. In the propolis group 15 individuals had crusted lesions on Day 3 compared to 8 individuals in the acyclovir group and none in the placebo group (p = 0.0006). On Day 7, 10 participants in the propolis group, 4 in the acyclovir group and 3 in the placebo group had healed. At the initial examination all patients had local symptoms and 28% general symptoms. At Day 3, 3 patients in the propolis group had local symptoms compared to 8 and 9 in the acyclovir and placebo groups respectively. Of the women, 66% had vaginal superinfections of microbial pathogens at the initial examination. In the acyclovir and placebo groups no change in the vaginal flora was found following treatment whereas in the propolis group the incidence of superinfection was reduced by 55%. (p = 0.10 n.s.). CONCLUSION: An ointment containing flavonoids appeared to be more effective than both acyclovir and placebo ointments in healing genital herpetic lesions, and in reducing local symptoms.     

Balm mint extract (Lo-701) for topical treatment of recurring herpes labialis.

A double-blind, placebo-controlled, randomized trial was carried out with the aim of proving efficacy of standardized balm mint cream [active ingredient: 1% Lo-701--dried extract from Melissa officinalis L. leaves (70:1)] for the therapy of herpes simplex labialis. Sixty six patients with a history of recurrent herpes labialis (at least four episodes per year) in one center were treated topically; 34 of them with verum and 32 with placebo. The cream had to be smeared on the affected area four times daily over five days. A combined symptom score of the values for complaints, size of affected area and blisters at day 2 of therapy was formed as the primary target parameter. There was a significant difference in the values of the primary target parameter between both treatment groups: verum 4.03 +/- 0.33 (3.0); placebo 4.94 +/- 0.40 (5.0); values given are mean +/- SEM (median) of the symptoms score on day 2 of therapy. The tested formulation is effective for the treatment of herpes simplex labialis. The significant difference in the combined symptom score on the second day of treatment is of particular importance having in mind that the complaints in patients suffering from herpes labialis are usually most intensive at that time. In addition to the shortening of the healing period, the prevention of a spreading of the infection and the rapid effect on typical symptoms of herpes like itching, tingling, burning, stabbing, swelling, tautness and erythema, the balm mint cream has a further advantage. The different mechanism of action of the balm mint extract rules out the development of resistance of the herpes virus. Some indication exists that the intervals between the periods with herpes might be prolonged with balm mint cream treatment.     

Application of an Optimized Tape Stripping Method for the Bioequivalence Assessment of Topical Acyclovir Creams

This study indicates the application of tape stripping (TS) for bioequivalence (BE) assessment of a topical cream product containing 5% acyclovir. A TS method, previously used successfully to assess BE of topical clobetasol propionate and clotrimazole formulations, was used to assess BE of an acyclovir cream (5%) formulation as well as a diluted acyclovir formulation (1.5%) applied to the skin of healthy humans. An appropriate application time was established by conducting a dose duration study using the innovator product, Zovirax® cream. Transepidermal water loss was measured and used to normalize thicknesses between subjects. The area under the curve (AUC) from a plot of amount of acyclovir/strip vs cumulative fraction of stratum corneum (SC) removed was calculated for each application site. BE was assessed using Fieller’s theorem in accordance with FDA’s guidance for assessment of BE of topical corticosteroids. Adco-acyclovir cream (5%) was found to be BE to Zovirax® cream, where the mean test/reference (T/R) ratio of the AUC’s was 0.96 and the bioequivalence interval using a 90% confidence interval was 0.91–1.01 with a statistical power >?95%, whereas the diluted test product fell outside the BE acceptance criteria with T/R ratio of AUC of 0.23 and a 90% CI of 0.20–0.26. This study indicates that the data resulting from the application of this TS procedure has reinforced the potential for its use to assess BE of topical drug products intended for local action, thereby obviating the necessity to undertake clinical trials in patients.     

Combined therapy of patients with recurring anogenital herpes infection

Up-to-date conceptions of etiology and epidemiology of anogenital herpetic infection are described. The main mechanisms of immunological shifts in subjects with anogenital Herpes infection are discussed. The efficacy and safety of cycloferon in the combined treatment of patients with recurring anogenital herptic infection were estimated. The clinical efficacy of the combined therapy (acyclovir in a dose of 200 mg 5 times a day for 5 days + cycloferon liniment applied topically on the eruptions twice a day for 5 days) was 85% or 25% higher vs. the control.     

磺胺嘧啶银混悬液联合银锌霜分阶段疗法在大面积烧伤中的应用

目的：观察2008年1月至2010年12月期间98例TBSA大于35%的烧伤病人创面联合应用磺胺嘧啶银混悬液联合银锌霜的疗效。方法：以同期76例应用碘伏的病人作为对照,两组病人的平均年龄、烧伤面积、Ⅲ度面积无显著差别,用药方式均以半暴露为主。结果：磺胺嘧啶银混悬液联合银锌霜组能显著增加细菌转阴率,减少抗生素应用时间及植皮手术次数,缩短愈合时间。结论：磺胺嘧啶银混悬液联合银锌霜较碘伏能显著增加抗感染能力,有利于肉芽创面形成,为自行愈合或再次手术打下良好基础,值得应用。     

Aluminium sucrose biscuit fillings to control hyperphosphataemia in patients undergoing dialysis.

Aluminium hydroxide is used to prevent hyperphosphataemia in patients undergoing dialysis, but many standard preparations are unpalatable. In this study hydrated aluminium sucrose was suspended in synthetic cream and used as a biscuit filling. Six patients undergoing dialysis took part in five five-week study periods comparing different forms of treatment. No significant difference was found between serum phosphate concentrations measured during standard treatment and those measured during treatment with aluminium sucrose biscuits. There was no significant difference in serum phosphate concentrations when the patients were given placebo biscuits and when they received no treatment. Aluminium sucrose presented in this form was an adequate phosphate binder and was acceptable to the patients.     

Acyclovir given as prophylaxis against oral ulcers in acute myeloid leukaemia: randomised,double blind,placebo controlled trial.

OBJECTIVES--To evaluate (a) the prophylactic effect of the antiherpetic drug acyclovir on oral ulcers in patients with acute myeloid leukaemia receiving remission induction chemotherapy and thus (b), indirectly, the role of herpes simplex virus in the aetiology of these ulcers. DESIGN--Randomised, double blind, placebo controlled trial. SUBJECTS--74 herpes simplex virus seropositive patients aged 18-84. Thirty seven patients received acyclovir (800 mg by mouth daily) and 37 placebo. The patients were examined daily for 28 days. MAIN OUTCOME MEASURES--Occurrence of herpes labialis, intraoral ulcers, and acute necrotising ulcerative gingivitis. RESULTS--The two populations were comparable in age, sex, type of antineoplastic treatment, and history of herpes labialis. Acute oral infections occurred in 25 of the acyclovir treated patients and 36 of the placebo treated patients (relative risk 0.69 (95% confidence interval 0.55 to 0.87)). This difference was due to a reduction in the incidence of herpes labialis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)), intraoral ulcers excluding the soft palate (one case versus 13 cases; relative risk 0.08 (0.01 to 0.56)), and acute necrotising ulcerative gingivitis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)). However, ulcers on the soft palate were diagnosed with similar frequency in the two groups. Isolation of herpes simplex virus type 1 in saliva was reduced from 15 cases in the placebo group to one case in the acyclovir group (relative risk 0.07 (0.01 to 0.48)). CONCLUSION--Intraoral ulcers excluding the soft palate are most often due to infection with herpes simplex virus, whereas ulcers on the soft palate have a non-herpetic aetiology. The findings suggest that acute necrotising ulcerative gingivitis may also be due to herpes simplex virus. Prophylaxis with acyclovir should be considered for patients with acute myeloid leukaemia during remission induction therapy.     

Protocol for German trial of Acyclovir and corticosteroids in Herpes-simplex-virus-encephalitis (GACHE): a multicenter, multinational, randomized, double-blind, placebo-controlled German, Austrian and Dutch trial [ISRCTN45122933]

Background

The treatment of Herpes-simplex-virus-encephalitis (HSVE) remains a major unsolved problem in Neurology. Current gold standard for therapy is acyclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains up to 15%, less than 20% of patients are able to go back to work, and the majority of patients suffer from severe disability. This is a discouraging, unsatisfactory situation for treating physicians, the disabled patients and their families, and constitutes an enormous burden to the public health services. The information obtained from experimental animal research and from recent retrospective clinical observations, indicates that a substantial benefit in outcome can be expected in patients with HSVE who are treated with adjuvant dexamethasone. But currently there is no available evidence to support the routine use of adjuvant corticosteroid treatment in HSVE. A randomized multicenter trial is the only useful instrument to address this question.

Design

GACHE is a multicenter, randomized, double-blind, placebo-controlled, parallel group clinical trial of treatment with acyclovir and adjuvant dexamethasone, as compared with acyclovir and placebo in adults with HSVE. The statistical design will be that of a 3-stage-group sequential trial with potential sample size adaptation in the last stage.

Conclusion

372 patients with proven HSVE (positive HSV-DNA-PCR), aged 18 up to 85 years; with focal neurological signs no longer than 5 days prior to admission, and who give informed consent will be recruited from Departments of Neurology of academic medical centers in Germany, Austria and The Netherlands. Sample size will potentially be extended after the second interim analysis up to a maximum of 450 patients.

Trial Registration

Current Controlled Trials ISRCTN45122933     

Antihirsutism activity of Fennel (fruits of Foeniculum vulgare) extract. A double-blind placebo controlled study.

Idiopathic hirsutism is defined as the occurrence of excessive male pattern hair growth in women who have a normal ovulatory menstrual cycle and normal levels of serum androgens. It may be a disorder of peripheral androgen metabolism. In this study we evaluated the clinical response of idiopathic hirsutism to topical Fennel extract. Fennel, Foeniculum vulgare, is a plant, which has been used as an estrogenic agent. The ethanolic extract of Fennel was obtained by using a soxhlete apparatus. In a double blind study, 38 patients were treated with creams containing 1%, 2% of Fennel extract and placebo. Hair diameter was measured and rate of growth was considered. The efficacy of treatment with the cream containing 2% Fennel is better than the cream containing 1% Fennel and these two were more potent than placebo. The mean values of hair diameter reduction was 7.8%, 18.3% and -0.5% for patients receiving the creams containing 1%, 2% and 0% (placebo) respectively.     

Comparison of In Vitro Release Rates of Acyclovir from Cream Formulations Using Vertical Diffusion Cells

Acyclovir, indicated in the treatment of herpes labialis (“cold sores”), is formulated as semisolid topical dosage forms and marketed in numerous countries. Since the formulations of the various acyclovir products may differ from country to country, this study was undertaken to compare the in vitro release of acyclovir from various generic cream products available on the South African and Indian markets using the respective brand/innovator product as the reference product. The in vitro studies were carried out using vertical diffusion cells with a diffusional surface area of 1.767 cm² and various commercially available membranes. Normal saline was used as receptor fluid and the temperature maintained at 32 ± 0.5°C. The in vitro release comparisons were based on the recommendations described in the US Food and Drug Administration Draft Guidance for acyclovir ointment and the SUPAC-SS Guidance for non-sterile semisolid dosage forms. The release rates (slope) of the test (T) and the relevant reference product (R) were monitored and compared. The comparative release of acyclovir from the various generic formulations compared with the reference product was found to be within the limits of 75–133.33% with a 90% confidence interval. These experiments indicate that the generic acyclovir cream formulations exhibited release rates that were comparable to the innovator product and could be considered to be bioequivalent.KEY WORDS: acyclovir cream, FDA Guidance, in vitro release, membranes, vertical diffusion cells     

Topical treatment of erectile dysfunction: randomised double blind placebo controlled trial of cream containing aminophylline,isosorbide dinitrate,and co-dergocrine mesylate.

OBJECTIVE--To examine the effectiveness in treating impotence to topically applied cream containing three vasodilators--aminophylline, isosorbide dinitrate, and co-dergocrine mesylate--which act by different mechanisms. DESIGN--Randomised double blinded placebo controlled crossover trial over two weeks. SUBJECTS--36 men with erectile dysfunction randomly allocated to two equal groups. INTERVENTIONS--Active cream containing aminophylline 3%, isosorbide dinitrate 0.25%, and co-dergocrine mesylate 0.05% for one week and placebo for another. MAIN OUTCOME MEASURES--Patients'' reported experience of penile responses and side effects of treatment in questionnaires. Penile tumescence and arterial flow in the laboratory. RESULTS--21 patients reported full erection and satisfactory intercourse with the active cream. Three men reported full erection and satisfactory intercourse with either cream. The active cream was more effective in psychogenic than organic impotence (eight out of nine men with psychogenic impotence achieved a full erection upsilon four out of eight with neurogenic impotence and two out of seven with arterial insufficiency). No major side effects were reported. In the laboratory the active cream increased penile arterial flow (0.19 (SD 0.08) m/s upsilon 0.02 (0.15) m/s with placebo) and induced tumescence in 24 patients. CONCLUSIONS--Topical treatment with a cream containing three different vasodilators might be considered before intracavernous injection of vasoactive agents, particularly in psychogenic impotence.     

First-dose analgesic effect of the cyclo-oxygenase-2 selective inhibitor lumiracoxib in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled comparison with celecoxib [NCT00267215]

Cyclo-oxygenase-2 selective inhibitors are frequently used to manage osteoarthritis. We compared the analgesic efficacy of the novel cyclo-oxygenase-2 selective inhibitor lumiracoxib (Prexige) versus placebo and celecoxib in patients with knee osteoarthritis. This seven day, double-blind, placebo and active comparator controlled, parallel group study included 364 patients aged > or = 50 years with moderate-to-severe symptomatic knee osteoarthritis. Patients received lumiracoxib 400 mg/day (four times the recommended chronic dose in osteoarthritis; n = 144), placebo (n = 75), or celecoxib 200 mg twice daily (n = 145). The primary variable was actual pain intensity difference (100 mm visual-analogue scale) between baseline and the mean of three hour and five hour assessments after the first dose. Actual pain intensity difference, average and worst pain, pain relief and functional status (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) were measured over seven days. Patients also completed a global evaluation of treatment effect at study end or premature discontinuation. For the primary variable, the superiority of lumiracoxib versus placebo, the noninferiority of lumiracoxib versus celecoxib, and the superiority of lumiracoxib versus celecoxib were assessed by closed test procedure adjusting for multiplicity, thereby maintaining the overall 5% significance level. In addition, celecoxib was assessed versus placebo in a predefined exploratory manner to assess trial sensitivity. Lumiracoxib provided better analgesia than placebo 3-5 hours after the first dose (P = 0.004) through to study end. The estimated difference between lumiracoxib and celecoxib 3-5 hours after the first dose was not significant (P = 0.185). Celecoxib was not significantly different from placebo in this analysis (P = 0.069). At study end 13.9% of lumiracoxib-treated patients reported complete pain relief versus 5.5% and 5.3% of celecoxib and placebo recipients, respectively. WOMAC total and subscales improved for both active treatments versus placebo except for difficulty in performing daily activities, for which celecoxib just failed to achieve significance (P = 0.056). In the patient's global evaluation of treatment effect, 58.1% of patients receiving lumiracoxib rated treatment as 'excellent' or 'good', versus 48.6% of celecoxib and 25.3% of placebo patients. Lumiracoxib was well tolerated. The overall incidence of adverse events was similar across treatment groups.     

Efficacy and safety of foscarnet for recurrent orolabial herpes: a multicentre randomized double-blind study.

Foscarnet sodium (trisodium phosphonoformate hexahydrate) has been shown to inhibit herpes simplex virus (HSV) in vitro and to be efficacious for topical treatment of experimental HSV infection in animals. To assess its clinical efficacy in the treatment of recurrent orolabial herpes a multicentre collaborative, double-blind, placebo-controlled trial was conducted. The study patients were randomly assigned to receive either 3% foscarnet cream (78 patients) or placebo (cream vehicle) (75 patients) and were asked to start treatment at the earliest indication of a recurrence. Efficacy was evaluated in 143 patients (74 in the foscarnet group and 69 in the placebo group). There was no significant difference in time to healing or duration of virus shedding between the two groups. However, in the subgroup of patients who started treatment before vesicles appeared, the duration of virus shedding was shorter in the foscarnet group than in the placebo group (p = 0.04), and the proportion of lesions that evolved to the vesicular stage was smaller (p = 0.03). No significant difference in the incidence of local or systemic adverse effects was noted between the two groups. We conclude that the beneficial effect of foscarnet was limited to a subgroup of patients who started treatment in the prevesicular stage.     

Twice weekly fluticasone propionate added to emollient maintenance treatment to reduce risk of relapse in atopic dermatitis: randomised,double blind,parallel group study

Objective To explore the efficacy and safety of fluticasone propionate, cream and ointment, applied twice weekly in addition to maintenance treatment with emollients, in reducing the risk of relapse of chronic recurrent atopic dermatitis.Design Randomised, double blind, parallel group study of 20 weeks'' duration.Setting Dermatology outpatient clinics (6 countries, 39 centres).Participants Adult (aged 12-65) patients with moderate to severe atopic dermatitis who were experiencing a flare.Methods Participants applied fluticasone propionate (0.05% cream or 0.005% ointment; once or twice daily) regularly for four weeks to stabilise their condition. The patients whose disease was brought under control then continued into a 16 week maintenance phase, applying emollient on a daily basis with a bath oil as needed and either the same formulation of fluticasone propionate or its placebo base (emollient alone) twice weekly to the areas that were usually affected.Main outcome measure Time to relapse of atopic dermatitis during maintenance phase.Results 376 patients entered the stabilisation phase, and 295 continued into the maintenance phase. After 16 weeks in the maintenance phase, the disease remained under control in 133 patients (87 using fluticasone propionate twice weekly, 46 using emollient alone), 135 (40 fluticasone propionate, 95 emollient) had experienced a relapse, and 27 had discontinued. Median time to relapse was six weeks for emollient alone compared with more than 16 weeks for additional fluticasone propionate. Patients who applied fluticasone propionate cream twice weekly were 5.8 times less likely (95% confidence interval 3.1 to 10.8, P < 0.001) and patients using fluticasone propionate ointment 1.9 times less likely (1.2 to 3.2, P=0.010) to have a relapse than patients applying emollient alone. The groups showed no differences in adverse events.Conclusion After atopic dermatitis had been stabilised the addition of fluticasone propionate twice weekly to maintenance treatment with emollients significantly reduced the risk of relapse.     

Topical Fat Reduction

The fat on women's thighs is more difficult to mobilize due to increased α-2 adrenergic receptor activity induced by estrogen. Lipolysis can be initiated through adipocyte receptor stimulation (β adrenergic) or inhibition (adenosine or α-2 adrenergic) or by inhibition of phosphodiesterase. Since many women desire regional thigh fat loss, a series of clinical trials were initiated using one thigh as a double-blinded control. Trial #1: Five overweight women had injections of isoproterenol at intervals around the thigh three times a week for 4 weeks with diet and walking. Trial #2: Five overweight woman had ointment containing forskolin, yohimbine and aminophylline applied to the thigh five times a week for 4 weeks after hypertonic warm soaks with a diet and walking. Trial #3: Eighteen overweight women were divided into three groups of six and trial #2 was repeated with each agent alone vs. placebo using forskolin, yohimbine or aminophylline in separate ointments. Trial #4: Thirty overweight women had 10% aminophylline ointment applied to the thigh five times a week for 6 weeks with diet and walking. Chemistry panel, theophylline level and patch testing wereperformed. Trial#5: Twelve women had trial #4 repeated with 2% aminophylline cream without a diet or walking. Trial #6: Trial #5 was repeated with 0.5% aminophylline cream. All trials except yohimbine ointment gave significantly more girth loss from the treated thigh (p < 0.05 to p < 0.001). Chemistry panel showed no toxicity. Theophylline was undetectable and patch testing was negative. We conclude that topical fat reduction for women's thighs can be achieved without diet or exercise.     

Successful treatment of experimental B virus (Herpesvirus simiae) infection with acyclovir.

The efficacy of the new nucleoside analogue acyclovir against B virus (Herpesvirus simiae) was investigated in rabbits and Vero cells infected with 2-136 and 0.3-1.0 TCD50 of the virus respectively. In the Vero cells 1 mg of acyclovir/1 reduced the yield of virus by 90%, which was slightly less than the effect on herpes simplex virus. Results in the rabbits varied with the interval between doses, duration of treatment, and delay before starting treatment. Acyclovir controlled an otherwise lethal infection when given not less than eight-hourly for 14 days. Withdrawing treatment after 9-10 days resulted in late-onset fatal disease in some rabbits. Treatment begun within 24 hours after infection gave complete protection, and rabbits first treated up to five days after infection showed a significant reduction in mortality (p less than 0.001). The plasma half life of acyclovir is twice as long in man as in rabbits and progression of the disease is much slower. Hence acyclovir may be useful for post-exposure prophylaxis against B virus infection in man and possibly also for treatment of the disease.     

Drug susceptibilities of isolates of varicella-zoster virus in a clinical study of oral brovavir

Susceptibilities to brovavir [1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)-uracil] and acyclovir of clinical isolates of varicella-zoster virus obtained from 58 patients with herpes zoster, included in a clinical trial of oral brovavir, were tested by a plaque reduction method. All 101 isolates were significantly susceptible to brovavir; 50% effective dose of brovavir for these isolates ranged between 0.6-4.0 ng/ml (average: 1.29 ng/ml). Brovavir was about 3,000 times more potent than acyclovir against these isolates. No marked change in the susceptibility of isolates from these patients during treatment with brovavir was observed.     

Inhalation of an Ethanol-Based Zileuton Formulation Provides a Reduction of Pulmonary Adenomas in the A/J Mouse Model

Potential efficacy of zileuton, a 5-LOX inhibitor, was evaluated for the reduction of pulmonary adenomas in the A/J murine model when administered via nose-only inhalation. Development of pulmonary adenomas was induced with benzo(a)pyrene. Animals were treated with a zileuton solution (5 mg/mL in 85:15 ethanol/water) either twice weekly or five times a week via nose-only inhalation; The placebo solution (85:15 EtOH/H₂O, no active) was also evaluated. Dose delivered was calculated to be 1.2 mg/kg per exposure for each zileuton group. After 20 weeks of treatment, surface tumors were enumerated and histologically assessed. A significant reduction in tumor count was noted for both the twice weekly administration (40%) and the five times a week administration (59%). The data also showed a significant reduction for the group, which received the placebo (approximately 58%). The treatment groups were also found to have an impact on the histological stages of adenoma development.