Effectiveness and safety of oral terbinafine for dermatophyte distal subungual onychomycosis.

INTRODUCTION: Terbinafine has been a cornerstone in dermatophyte infection treatment. Despite its global efficacy, the emergence of terbinafine resistance raises concerns, requiring ongoing vigilance. AREAS COVERED: This paper focuses on evaluating the efficacy and safety of terbinafine in treating dermatophyte toenail infections. Continuous and pulse therapies, with a 24-week continuous regimen and a higher dosage of 500 mg/day have demonstrated superior efficacy to the FDA approved regimen of 250 mg/day x 12 weeks. Pulse therapies, though showing comparable effectiveness, present debates with regards to their efficacy as conflicting findings have been reported. Safety concerns encompass hepatotoxicity, gastrointestinal, cutaneous, neurologic, hematologic and immune adverse-effects, and possible drug interactions, suggesting the need for ongoing monitoring. EXPERT OPINION: Terbinafine efficacy depends on dosage, duration, and resistance patterns. Continuous therapy for 24 weeks and a dosage of 500 mg/day may enhance outcomes, but safety considerations and resistance necessitate individualized approaches. Alternatives, including topical agents and alternative antifungals, are to be considered for resistant cases. Understanding the interplay between treatment parameters, adverse effects, and resistance mechanisms is critical for optimizing therapeutic efficacy while mitigating resistance risks. Patient education and adherence are vital for early detection and management of adverse effects and resistance, contributing to tailored and effective treatments.

The safety of oral antifungals for the treatment of onychomycosis.

INTRODUCTION: Oral antifungals are used for the treatment of moderate-severe onychomycosis. Terbinafine and itraconazole are approved for onychomycosis treatment in North America; additionally, fluconazole is indicated for onychomycosis in Europe. Other oral antifungals such as ketoconazole and griseofulvin are no longer used for the treatment of onychomycosis due to safety concerns and relatively lower efficacy. SEARCH STRATEGY: On 7 March 2023, we conducted a comprehensive search in PubMed and Google Scholar, while also manually examining selected article bibliographies and package inserts. AREAS COVERED: Terbinafine, itraconazole, and fluconazole have several interactions with cytochrome-p450, and either alone, or when co-administered with other drugs these interactions can facilitate a multitude of adverse events. This article identifies possible hepatic, renal, cutaneous, cardiovascular, neurological, hemopoietic, and obstetric adverse events. We have also compared the rates of hepatotoxicity, clinically apparent liver injury, and alanine transaminase elevations between oral antifungals, and recommendations for hepatic monitoring. EXPERT OPINION: We recommend laboratory testing of liver function tests prior to the administration of any oral antifungals, especially when clinically indicated. In the event of a first treatment failure, the diagnosis of onychomycosis must be confirmed, and consideration given to antifungal susceptibility testing. Antifungal stewardship will help reduce the incidence of antifungal resistance.

Relative impact of traditional vs. newer oral antifungals for dermatophyte toenail onychomycosis: a network meta-analysis study.

BACKGROUND: There is a paucity of evidence regarding the relative therapeutic efficacy of treatments for onychomycosis. OBJECTIVES: We determined the relative efficacy of monotherapies for dermatophyte toenail onychomycosis with Bayesian network meta-analyses (NMAs). METHODS: We searched PubMed, Scopus, EMBASE (Ovid) and CINAHL to identify studies that investigated the efficacy of monotherapy with oral antifungals for dermatophyte toenail onychomycosis in adults. In this paper, 'regimen' corresponds to a given agent and its dosage. The relative effects and surface under the cumulative ranking curve (SUCRA) values of the various regimens were estimated; evidence quality was assessed at the study level and across networks. RESULTS: Data from 21 studies were used. Our two efficacy-related endpoints were: (i) mycological and (ii) complete cure at 1 year; safety--related endpoints were: (i) 1-year count of any adverse event (AE), (ii) 1-year odds of discontinuation due to any AE, (iii) 1-year odds of discontinuation due to liver issues. Thirty-five regimens were identified; the newer agents among these included posaconazole and oteseconazole. We compared the efficacy of newer regimens with traditional ones like 'terbinafine 250 mg daily for 12 weeks' and 'itraconazole 200 mg daily for 12 weeks. We found that an agent's dosage was associated with its efficacy; for example, the 1-year odds of mycological cure with terbinafine 250 mg daily for 24 weeks (SUCRA = 92.4%) were significantly greater than those of terbinafine 250 mg daily for 12 weeks (SUCRA = 66.3%) (odds ratio 2.62, 95% credible interval 1.57-4.54). We also found that booster regimens can increase efficacy. Our results showed that some triazoles could be more effective than terbinafine. CONCLUSIONS: This is the first NMA study of monotherapeutic antifungals - and their various dosages - for dermatophyte toenail onychomycosis. Our findings could provide guidance for the selection of the most appropriate antifungal agent, especially amid the growing concerns about terbinafine resistance.

All in a scent - naphthalene dependence confined to pregnancy: a case report.

BACKGROUND: Inhalant or volatile substance use is a health issue with significant medical and psychiatric sequelae. Inhalants or volatile substances are volatile organic substances found in domestic and commercial products which are inhaled to obtain pleasurable effects. They are easily accessible, cheap, and legal. Common inhalants are spray, paints, glue and shoe polish whilst naphthalene or 'mothball' abuse is reported less commonly. We report a case of a 29-year-old female who inhaled and ingested naphthalene during her pregnancy. This case report is unique because the dependence on naphthalene was confined to pregnancy and resolved as soon as she delivered. This brings up the question whether pregnancy in general increases the risk of substance dependence in vulnerable populations or whether the dependence in this patient during pregnancy is due to individual factors. CASE PRESENTATION: The patient we report is a 29-year-old female who developed a strong desire to inhale mothballs during her third pregnancy. The pattern of use started in the first trimester meeting the criteria for dependence syndrome and resolved completely by the second day following delivery. She had features suggestive of harmful use in her second pregnancy as well. CONCLUSIONS: The case report emphasizes that pregnant women should be screened for psychoactive substance use. Equally important is the need for adequate psychoeducation about the myths and cultural beliefs associated with pregnancy-related cravings and the potentially devastating consequences of harmful cravings on the neonate and the mother. The case highlights how chemicals used in day-to-day activities can lead to dependence.

A Systematic Review and Meta-analysis of Efficacy and Safety of Calcimimetic Agents in the Treatment of Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease.

BACKGROUND: Some reports have pointed out that calcimimetics agents are effective in the treatment of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) patients, but there is no detailed description of the advantages and disadvantages of calcimimetics agents of SHPT in CKD patients. We tried to pool the published data to verify the effectiveness of calcimimetics agents and to compare the advantages and disadvantages of cinacalcet compared with control in the treatment of SHPT in CKD patients. METHODS: We included eligible studies of published papers from January 1st, 2000 to December 31st, 2020 in Medline, Pubmed and Web of science databases, and the data were extracted for this meta-analysis. RESULTS: Twenty-seven studies were eligible, and all the included studies were randomized controlled trials (RCT) including patients treated with long-term dialysis. The results indicated that calcimimetic agents can reduce the parathyroid hormone (PTH, pg/ml) level (WMD = -178.22, 95% CI: -238.57, -117.86, P < 0.00001), calcium (Ca, mg/dl) level (WMD = -0.71, 95% CI: -0.86, -0.55, P < 0.00001), phosphorus (P, mg/dl) level (WMD = -0.32, 95% CI: -0.55, -0.08, P = 0.008), calcium-phosphorus product level (WMD = -7.73, 95% CI: -9.64, -5.82, P < 0.00001). Calcimimetic agents increased the bone alkaline phosphatase (BSAP, ng/ml) levels and rate of achieving target PTH, and reduced osteocalcin levels and the rate of parathyroidectomy. Calcimimetic agents increased the total adverse events' rate, the rate of hypocalcemia and gastrointestinal side effects (nausea, vomiting, abdominal pain and diarrhea), but there was no significant difference in serious adverse events between the calcimimetic agent group and control group. CONCLUSION: Calcimimetic agents can reduce the PTH level, Ca level, P level, calcium-phosphorus product level and do not increase serious adverse events.

Pharmacokinetics, pharmacodynamics, and safety of verinurad with and without allopurinol in healthy Asian, Chinese, and non-Asian participants.

Verinurad is a selective inhibitor of uric acid transporter 1 (URAT1). Here, we assessed the safety, pharmacokinetics, and pharmacodynamics of verinurad + allopurinol and verinurad monotherapy in healthy participants. Studies 1 (NCT03836599) and 2 (NCT02608710) were randomized Phase 1 studies. In Study 1, 12 healthy Asian participants received 24 mg verinurad + 300 mg allopurinol or placebo, and 9 healthy Chinese participants received 12 mg verinurad + 300 mg allopurinol. In Study 2, 24 healthy non-Asian male participants received 12 mg verinurad. Safety analyses included assessment of adverse events (AEs). Pharmacokinetic parameters included maximum concentration (Cmax ) and area under plasma concentration-time curve (AUC) over 24 h (AUCτ ). Pharmacodynamic parameters included percentage change from baseline (day -1) in serum uric acid (sUA) and urinary uric acid (uUA). There were no serious AEs or deaths in either study. In Study 1, steady-state geometric mean (gCV%) Cmax and AUCτ values of verinurad after 7 days' dosing were 73.6 (29.0) ng/mL and 478 (18.4) ng·h/mL, respectively, in healthy Asian participants, and 42.0 (40.1) ng/mL and 264 (36.1) ng·h/mL, respectively, in healthy Chinese participants; in Study 2, gCV% values were 36.3 (36.5) ng/mL and 271 (31.0) ng·h/mL, respectively. sUA decreased and uUA excretion increased compared with baseline following verinurad + allopurinol (Study 1) or verinurad (Study 2). When accounting for dose, the steady-state pharmacokinetics of verinurad following multiple dosing were comparable between healthy Asian and Chinese participants and healthy non-Asian participants. Verinurad treatments were well tolerated, including at higher verinurad exposures than previously evaluated after repeated dosing.

Results from a Phase 1/2 trial of BB2603, a terbinafine-based topical nano-formulation, in onychomycosis and tinea pedis.

BB2603 is a nano-formulation of the antifungal drug terbinafine with the polymer polyhexamethylene biguanide (PHMB) as an excipient to enhance solubility and drug delivery to skin and nails. BB2603 is delivered topically using a low-velocity spray. It is being developed in different strength formulations for the treatment of fungal infections of the nail and skin, including onychomycosis and tinea pedis, with BB2603-1 (0.01% terbinafine) tested in the present trial. The aim of this study was to assess systemic exposure, safety and tolerability of BB2603-1 compared with Lamisil® AT 1% spray and BB2603-1 vehicle control in onychomycosis and tinea pedis. Preliminary mycological and clinical activity were also investigated. This was a single-centre Phase 1/2, randomised, partially blinded, active- and vehicle-controlled, parallel-group trial in 46 subjects with onychomycosis associated with tinea pedis. Part 1 investigated BB2603-1 versus Lamisil AT 1% spray and BB2603-1 vehicle (4 weeks treatment). Part 2 investigated BB2603-1 versus BB2603-1 vehicle (additional 48 weeks treatment). No measurable systemic exposure of terbinafine was shown over 52 weeks of treatment with BB2603-1. BB2603-1 had an excellent safety and tolerability profile with no drug-related safety findings and no evidence of skin sensitisation. BB2603-1 showed preliminary evidence of anti-dermatophyte activity, demonstrated by a reduction in dermatophyte positive cultures and a reduction in microscopic evidence of dermatophytes. The pharmacokinetic, safety and efficacy data from this trial support further development of the topical terbinafine-based nano-formulation BB2603 in fungal infections of the skin and nail, including onychomycosis and tinea pedis.

[Evaluation of the efficacy of dapoxetine in primary and secondary forms of premature ejaculation].

OBJECTIVE: to compare the efficacy of dapoxetine in treatment of primary and secondary premature ejaculation. MATERIALS AND METHODS: The study included 60 patients with premature ejaculation (PE). Depending on the form of premature ejaculation they were divided into two groups: 27 patients with primary PE (group 1) and 33 patients with secondary PE (group 2). Patients were recommended to take dapoxetine 30 mg 1 hour before intercourse. A follow-up visit was scheduled on day 30 after receiving the drug. The intravaginal ejaculation latency time (IELT) and the Premature ejaculation diagnostic tool (PEDT) score were evaluated before dapoxetine was given and after 30 days from the start of the study. The significance of differences between baseline and follow-up values were compared using Wilcoxons test. In both groups, the proportion of patients with an incomplete response (IELT less than 2 minutes, PEDT more than 10) to symptomatic therapy with dapoxetine was evaluated. The proportion of patients with incomplete response to therapy was compared using the chi-square test. RESULTS: The median IELT among all patients before starting therapy was 63 seconds (interquartile interval [IQR]: 28.75-94). After one month of therapy median IELT increased to 119 seconds (IQR: 58.75-321.75). Median PEDT score was 16 (IQR: 13-19) at baseline and 7 (IQR: 4-12) at follow-up. In group 1, the median IELT increased from 57 to 83 seconds (p = 0.02088), and in group 2, the median IELT increased from 70 to 173 seconds (p<0.00001). The mean PEDT score decreased to 7 in both groups (p<0.00001). Incomplete response to therapy was observed in 66.7% of patients in group 1 and in 39.4% of patients in group 2. The difference between two groups was statistically significant (p=0.035456). CONCLUSION: Symptomatic therapy with dapoxetine has a positive effect on the intravaginal ejaculation latency time and patient satisfaction in both primary and secondary premature ejaculation. However, the incidence of incomplete response to therapy is higher in patients with primary premature ejaculation, which may be due to characteristic differences in the pathogenesis of primary and secondary premature ejaculation.

Allergic contact dermatitis from dyes used in the temple of spectacles.

BACKGROUND: We observed an increasing number of patients who presented with facial or retro-auricular dermatitis after skin contact with plastic spectacles or plastic covered temples. OBJECTIVES: To identify the allergens in plastic spectacles that may cause allergic contact dermatitis. METHODS: All patients with suspected allergic contact dermatitis to eyewear were tested with Solvent Orange 60 (SO60), four additionally with Solvent Yellow 14 (SY14), and five with scrapings from their own spectacles. In one case, a chemical analysis of the spectacles was performed to uncover the causative allergen. RESULTS: Three patients were allergic to SO60, two patients to SY14, and two patients were allergic to both SO60 and SY14. CONCLUSION: Patients with suspected allergic contact dermatitis from spectacles should be tested with SO60 and SY14, and based on findings from previous reports, also with Solvent Red 179.

A topical gel of tea tree oil nanoemulsion containing adapalene versus adapalene marketed gel in patients with acne vulgaris: a randomized clinical trial.

Adapalene is used for treatment of acne vulgaris, a common dermatological disease. Nano-based carriers have been developed to improve solubility and bioavailability of adapalene and other acne treatment drugs. In our previous report, tea tree oil nanoemulsion containing adapalene gel (TTO NE + ADA Gel) showed appropriate physical and biological properties such as stability, viscosity, pH, size, morphology and biocompatibility in an animal model. The present study was designed to assess efficacy and safety of the TTO NE + ADA Gel in comparison with 0.1% adapalene marketed gel (ADA Marketed Gel). A total of 100 patients were randomized to receive TTO NE + ADA Gel or ADA Marketed Gel, once daily at night, for 12 weeks. Analysis for efficacy was conducted by acne lesion count (total, inflammatory and non-inflammatory) and acne severity index at weeks 4, 8 and 12 using generalized estimating equation along with the safety assessments in each measurement for assessing dryness, erythema, burning sensation and irritation. Significantly better reduction in total, inflammatory, and non-inflammatory acne lesions were reported for TTO NE + ADA Gel as compared to the ADA Marketed Gel overall and on each measurement occasion (p value < 0.001 for all). Mean acne severity index also reduced with TTO NE + ADA Gel significantly in comparison with ADA Marketed Gel (p value < 0.001). Dryness was the most common adverse effect reported in both groups and it was higher in TTO NE + ADA Gel group. In conclusion, TTO NE + ADA Gel compared to ADA Marketed Gel appears more effective in the treatment of acne vulgaris, with no important change in adverse effects.

Safe Use of Adapalene 0.1 % Gel in a non-Prescription Environment.

BACKGROUND: Topical retinoids are the mainstay of acne therapy and, until 2016, were only available by prescription. The margin of safety (MOS) of adapalene for potential teratogenic effects, and its use in pregnancy were investigated as part of the OTC switch. OBJECTIVE: To determine MOS using a maximal usage trial (MUsT) and animal embryo-fetal development studies. To conduct a thorough review of safety data with respect to use of Adapalene 0.1% Gel during pregnancy. METHODS: The MUsT was multicenter, open-label pharmacokinetic study which enrolled adolescents and adult subjects with mainly severe acne vulgaris. The no observable adverse event level (NOAEL) for adapalene teratogenicity was established in rat and rabbit embryo-fetal development studies. An exhaustive review of pregnancy data from multiple safety databases was conducted. RESULTS: The calculated MOS for teratogenicity was 70 for Adapalene 0.1% Gel. For the pregnancy safety review, no pregnancy malformations were attributable to topical adapalene use. LIMITATIONS: Animal studies do not always predict effects in human development. Additionally, safety data is voluntarily reported and intrinsically incomplete. CONCLUSION: Adapalene has a large and reassuring MOS making it suitable for OTC use. No teratogenic risk was identified in a MUsT and Pregnancy Safety Review. Adapalene 0.1% Gel is a safe and effective medication for the treatment of acne in a non-prescription environment. Based on available evidence, use of adapalene during pregnancy does not pose harm to the fetus. J Drugs Dermatol. 2021;20(12):1330-1335. doi:10.36849/JDD.6527.

Formulation and evaluation of butenafine loaded PLGA-nanoparticulate laden chitosan nano gel.

The present research work is designed to prepare and optimize butenafine (BT) loaded poly lactic co glycolic acid (PLGA) nanoparticles (BT-NPs). BT-NPs were prepared by emulsification probe sonication method using PLGA (A), PVA (B) as polymer and stabilizer, respectively. The optimum composition of BT-NPs was selected based on the point prediction method given by the Box Behnken design software. The optimized composition of BT-NPop showed a particle size of 267.21 ± 3.54 nm with an entrapment efficiency of 72.43 ± 3.11%. The optimum composition of BT-NPop was further converted into gel formulation using chitosan as a natural polymer. The prepared topical gel formulation (BT-NPopG) was further evaluated for gel characterization, drug release, permeation study, irritation, and antifungal studies. The prepared BT-NPopG formulation showed optimum pH, viscosity, spreadability, and drug content. The release and permeation study results revealed slow BT release (42.76 ± 2.87%) with significantly enhanced permeation across the egg membrane. The irritation study data showed negligible irritation with a cumulative score of 0.33. The antifungal study results conclude higher activity than marketed as well as pure BT. The overall conclusion of the results revealed BT-NPopG as an ideal delivery system to treat topical fungal infection.

Terbinafine used safely in autoimmune hepatitis for treatment of tinea corporis.

Terbinafine is often considered contraindicated in those with liver disease, as one of the known side effects is hepatotoxicity. We report the first case documenting the safe use of oral terbinafine in a 77-year-old woman with stable autoimmune hepatitis presenting with extensive tinea corporis. Precautions were carried out to minimise the risk of worsening hepatotoxicity, including consultation with the patient's hepatologist, limiting terbinafine exposure to less than 6 weeks, monitoring of liver function tests, and patient education. The patient's fungal infection cleared without any signs or symptoms of worsening liver disease. The rash had not recurred 6 months after treatment. When terbinafine must be used in a patient with pre-existing liver disease, we recommend considering a short course of oral terbinafine after consultation with their hepatologist, obtaining baseline liver function tests with consideration of further monitoring during treatment course, and patient education on the signs and symptoms of liver injury.

Topical NAVS naphthalan for the treatment of oral lichen planus and recurrent aphthous stomatitis: A double blind, randomized, parallel group study.

AIM: To evaluate the effectiveness of non-aromatic very rich in steranes (NAVS) naphthalan in the treatment of oral lichen planus (OLP) and recurrent aphthous stomatitis (RAS). Null hypothesis was that there would be no difference between NAVS and topical steroids in the treatment of OLP and RAS. METHODS: The study consisted of two sub-trials conducted as randomized, double-blind controlled studies: first included OLP patients and second patients with RAS. Patients received either NAVS or 0.05% betamethasone dipropionate. Primary outcomes were activity score (OLP patients), No of lesions and lesion diameter (RAS patients) and pain intensity (VAS) while secondary outcome included the impact of the disease on quality of life assessed by Oral health impact profile (OHIP 14). RESULTS: No significant differences in terms of OLP clinical signs (p = 0.84, η2 = 0.001) and responses on the OHIP-14 (p = 0.81, η2 = 0.002) or on VAS (p = 0.14, η2 = 0.079) between NAVS and betamethasone groups were observed. In RAS patients, no significant differences between the groups in terms of lesion number (at days 3 and 5, p = 0.33 and p = 0.98, respectively), lesion diameter (days 3 and 5, p = 0.24 and p = 0.84, respectively) were observed. However, in NAVS group a significant reduction of lesions diameter was observed on the 3rd day, while in betamethasone group a significant reduction in lesions diameter was evident only after the 5th day. No significant differences in VAS (p > 0.05) and the OHIP-14 (p > 0.05) between groups were found. CONCLUSION: No evidence of differences between the two compared interventions was found. REGISTRATION: Retrospective registration of this trial was conducted in ClinicalTrials.gov on September 30, 2016; trial registration number: NCT02920658. https://clinicaltrials.gov/ct2/show/NCT02920658?term=NAVS&draw=2&rank=4.

Behavioral Effects of Developmental Exposure to JWH-018 in Wild-Type and Disrupted in Schizophrenia 1 (disc1) Mutant Zebrafish.

Synthetic cannabinoids can cause acute adverse psychological effects, but the potential impact when exposure happens before birth is unknown. Use of synthetic cannabinoids during pregnancy may affect fetal brain development, and such effects could be moderated by the genetic makeup of an individual. Disrupted in schizophrenia 1 (DISC1) is a gene with important roles in neurodevelopment that has been associated with psychiatric disorders in pedigree analyses. Using zebrafish as a model, we investigated (1) the behavioral impact of developmental exposure to 3 µM 1-pentyl-3-(1-naphthoyl)-indole (JWH-018; a common psychoactive synthetic cannabinoid) and (2) whether disc1 moderates the effects of JWH-018. As altered anxiety responses are seen in several psychiatric disorders, we focused on zebrafish anxiety-like behavior. Zebrafish embryos were exposed to JWH-018 from one to six days post-fertilization. Anxiety-like behavior was assessed using forced light/dark and acoustic startle assays in larvae and novel tank diving in adults. Compared to controls, both acutely and developmentally exposed zebrafish larvae had impaired locomotion during the forced light/dark test, but anxiety levels and response to startle stimuli were unaltered. Adult zebrafish developmentally exposed to JWH-018 spent less time on the bottom of the tank, suggesting decreased anxiety. Loss-of-function in disc1 increased anxiety-like behavior in the tank diving assay but did not alter sensitivity to JWH-018. Results suggest developmental exposure to JWH-018 has a long-term behavioral impact in zebrafish, which is not moderated by disc1.

Terbinafine Hydrochloride Combined With Itraconazole for Fungal Skin Diseases: A Randomized Controlled Trial.

BACKGROUND: Terbinafine and itraconazole are the common antifungal drugs in clinic. In vitro experiments proved that terbinafine combined with itraconazole achieves better antifungal effects. However, clinical study addressing this issue was still scarce. STUDY QUESTION: Terbinafine combined with itraconazole achieves better therapeutic effects in fungal skin diseases. STUDY DESIGN: Approximately 178 patients with fungal skin diseases from Meizhou People's Hospital, China, between October 2016 and October 2017 were admitted to this study. Patients were randomly distributed to 3 groups by randomly selecting random numbers and were treated with terbinafine, itraconazole, monotherapy, or combined therapy. Both patients and study investigators were unaware of grouping situations during experiments. Fifteen patients were excluded due to poor compliance, and 11 patients were excluded due to incomplete data. Finally, 152 patients were analyzed for this study. MEASURES AND OUTCOMES: The therapeutic effects were evaluated by clinic symptom scores, mycology examination, the cure rate, and the cure time. Adverse events, relapse of disease, and patient's satisfaction level were recorded during follow-up. RESULTS: In the terbinafine + itraconazole group, at 14 days after treatment, the symptom scores were significantly decreased, compared with the terbinafine or itraconazole group (P1 < 0.05, P2 < 0.05). At 28 days after treatment, the fungal infection of 37 patients was eradicated, which were significantly more than 26 patients in the terbinafine group and 19 patients in the itraconazole group (P1 < 0.05, P2 < 0.05). The terbinafine + itraconazole group also exhibited 100% cure rate of patients with fungal skin diseases, shorter cure time, and increased number of cured patients during the same treatment period, which was better than terbinafine or itraconazole monotherapy (P1 < 0.05, P2 < 0.05). In addition, no adverse events and no relapse of fungal disease were reported in the terbinafine + itraconazole group during follow-up. Ninety-eight percent patients were satisfied with the therapeutic effects of combined treatment. CONCLUSIONS: Compared with terbinafine or itraconazole monotherapy, terbinafine + itraconazole combined treatment achieves better therapeutic effects in fungal skin diseases.

Pharmacokinetics and Safety of Dapoxetine Hydrochloride in Healthy Chinese Men: Impact of Dose and High-Fat Meal.

Dapoxetine is the first oral medication specifically developed for the on-demand treatment of premature ejaculation. The pharmacokinetics and safety of 30 mg (n = 40) and 60 mg (n = 38) dapoxetine in healthy Chinese under fasted and fed states were assessed in 2 studies. Both studies are random, single-center, 2-period, open-label, 2-way crossover designs. Plasma concentration of dapoxetine was determined by high-performance liquid chromatography-tandem mass spectrometry, and the pharmacokinetic parameters were calculated using noncompartmental analysis. Dapoxetine was quickly absorbed and reached maximum concentration 1 to 3 hours after oral administration. Elimination was biphasic, and the plasma concentration decreased to 3% to 7% of maximum concentration by 24 hours while half-life was 15 to 18 hours. Meantime, high-fat meals slightly increased its exposure. Both doses of dapoxetine were well tolerated. The adverse events in the high-dose group under fasted and fed states were 37.9% and 19.0%, respectively.

The effect of evocalcet on vagus nerve activity of the gastrointestinal tract in miniature pigs.

Evocalcet is a novel calcimimetic agent with fewer gastrointestinal (GI) adverse effects compared to cinacalcet. Although it is thought that cinacalcet induces GI side effects through the direct stimulation of the calcium receptor (CaR) expressed in the GI tract, the differences in the direct stimulatory effects of these two drugs on the GI tract have not been reported. In this study, we analyzed the difference in the GI effects of these two calcimimetic agents using miniature pigs by detecting vagus nerve stimulation after oral administration of the agents. Although cinacalcet induced vomiting in miniature pigs, evocalcet never induced emetic symptoms. A significant increase in the vagus nerve action potentials was observed after the administration of cinacalcet. Although the increase of that after the administration of evocalcet was mild and not significant in comparison to that in the vehicle group, it was not significantly different from the vagus nerve action potentials after cinacalcet treatment.