Comparison of the Effectiveness and Safety of Clozapine Between Once-Daily and Divided Dosing Regimen in Patients With Treatment-Resistant Schizophrenia.

BACKGROUND: Clozapine is the most effective antipsychotic with respect to the incidence of discontinuation and is indicated for treatment-resistant schizophrenia. Although the recommendation for clozapine administration is divided dosing, once-daily dosing of clozapine is commonly prescribed in many countries. However, there is currently no clinical data comparing all-cause discontinuation between the 2 methods of administration of clozapine. OBJECTIVES: To compare the all-cause discontinuation and safety of clozapine administration between once-daily and divided dosing regimens. METHODS: This was a retrospective cohort study. Participants were patients with treatment-resistant schizophrenia who had received 300 to 600 mg/day of clozapine for at least 3 months. Data were collected from outpatient medical records at Somdet Chaopraya Institute of Psychiatry. Eligible patients were classified into 2 groups: once-daily dosing and divided dosing. The primary outcome was the all-cause discontinuation rate between groups. The duration of the study was 2 years. RESULTS: One hundred eighteen patients were included and analyzed in this study (once-daily dosing group: n = 58; divided dosing group: n = 60). There was no significant difference in all-cause discontinuation between the 2 groups (odds ratio 1.03; 95% confidence interval: [0.28, 3.79]: P = 1.00), or adverse events between groups. CONCLUSION AND RELEVANCE: In patients with treatment-resistant schizophrenia, there were no significant differences in effectiveness or safety between once-daily and divided dosing of clozapine. Further prospective studies with larger sample sizes are required to confirm these findings.

Evaluation of once-daily dosing and target concentrations in therapeutic drug monitoring for arbekacin: A meta-analysis.

INTRODUCTION: Arbekacin is the first aminoglycoside antibacterial agent approved for treating methicillin-resistant Staphylococcus aureus infection in Japan. Although therapeutic drug monitoring (TDM) is recommended during arbekacin treatment, little evidence for the target exposure and once-daily dosing has been reported. This study aimed to clarify the target peak/trough concentrations and the effectiveness of once-daily dosing of arbekacin against nephrotoxicity or treatment failure via meta-analysis. METHODS: A literature search was performed using MEDLINE, Cochrane Library, and Ichushi-Web. RESULTS: Nine observational cohort studies met the inclusion criteria. A peak arbekacin concentration of ≥15-16 µg/mL did not exhibit a statistically significant lower risk of treatment failure (risk ratio [RR] = 0.61, 95% confidence interval [CI] = 0.30-1.24). A trough arbekacin concentration of <2 µg/mL resulted in a significantly lower risk of nephrotoxicity (RR = 0.30, 95% CI = 0.15-0.61). Once-daily dosing significantly reduced the risk of treatment failure (RR = 0.61, 95% CI = 0.39-0.97) but not nephrotoxicity (RR = 0.54, 95% CI = 0.16-1.75). CONCLUSIONS: Once-daily dosing can improve the therapeutic efficacy of arbekacin, and a trough arbekacin concentration of <2 µg/mL can reduce the risk of nephrotoxicity. A peak arbekacin concentration of ≥15-16 µg/mL did not exhibit the significant lower risk of treatment failure. Additional clinical trials are required to confirm these findings.

Metformin extended-release versus immediate-release: An international, randomized, double-blind, head-to-head trial in pharmacotherapy-naïve patients with type 2 diabetes.

This international, randomized, double-blind trial (NCT01864174) compared the efficacy and safety of metformin extended-release (XR) and immediate-release (IR) in patients with type 2 diabetes. After a 4-week placebo lead-in, pharmacotherapy-naïve adults with glycated haemoglobin (HbA1c) at 7.0% to 9.2% were randomized (1:1) to receive once-daily metformin XR 2000 mg or twice-daily metformin IR 1000 mg for 24 weeks. The primary endpoint was change in HbA1c after 24 weeks. Secondary endpoints were change in fasting plasma glucose (FPG), mean daily glucose (MDG) and patients (%) with HbA1c <7.0% after 24 weeks. Overall, 539 patients were randomized (metformin XR, N = 268; metformin IR, N = 271). Adjusted mean changes in HbA1c, FPG, MDG and patients (%) with HbA1c <7.0% after 24 weeks were similar for XR and IR: -0.93% vs -0.96%; -21.1 vs -20.6 mg/dL (-1.2 vs -1.1 mmol/L); -24.7 vs -27.1 mg/dL (-1.4 vs -1.5 mmol/L); and 70.9% vs 72.0%, respectively. Adverse events were similar between groups and consistent with previous studies. Overall, metformin XR demonstrated efficacy and safety similar to that of metformin IR over 24 weeks, with the advantage of once-daily dosing.

Identification of selective 8-(piperidin-4-yloxy)quinoline sulfone and sulfonamide histamine H1 receptor antagonists for use in allergic rhinitis.

A series of potent, selective and long-acting quinoline-based sulfonamide human H1 histamine receptor antagonists, designed for once-daily intranasal administration for the treatment of rhinitis were developed. Sulfonamide 33b had a slightly lower affinity for the H1 receptor than azelastine, had low oral bioavailability in the rat and dog, and was turned over to five major metabolites. Furthermore, 33b had longer duration of action than azelastine in guinea pigs, lower rat brain-penetration, and did not cause time dependent inhibition of CYP2D6 or CYP3A4. The clinical dose in humans is expected to be low (approximately 0.5mg per day) based on the clinical dose used for azelastine and a comparison of efficacy data from animal models for 33b and azelastine.

Formulation of venlafaxine for once daily administration using polymeric material hybrids.

OBJECTIVE: Controlled release venlafaxine for once daily administration. METHODS: Drug resin complexation followed by polymer encapsulation. A 4(1).2(1) factorial design was used to study the effect of polymer type and core: coat ratio on the release profile and kinetics. Polymer combinations were tried for optimisation adapting the desIMNCility function. The optimised formula was tested in rabbits against commercial extended release capsules. RESULTS: Poly-epsilon-caprolactone, poly(d, l-lactide-co-glycolide) ester and poly(d, l-lactide) ester polymers were more efficient in lowering the release rate and the initial burst release than Eudragit(®)RS100. Encapsulation at 1:1 ratio ensured complete coats and drug release sustainment. Formula prepared using 50:50 PLA/Eudragit at 1:1 ratio sustained the drug release up to 24 h with low burst release. This formula had higher venlafaxine absorption in rabbits compared to the commercial capsules. CONCLUSIONS: The optimised formula is superior to the available once-daily trials regarding enhanced bioavailability, dosage form versatility and ease of scaling up.

Optimal Once-Daily Busulfan Administration in Pediatric Patients: A Simulation-Based Investigation of Intravenous Infusion Times.

Purpose: Pediatric patients receiving hematopoietic stem cell transplantation undergo regular administration of intravenous busulfan as a conditioning regimen. Once-daily regimen of busulfan has been proposed as a more convenient alternative to the traditional regimen, but it may increase the risk of toxicity such as veno-occlusive disease (VOD). The study aims to evaluate the pharmacokinetics (PKs) of once-daily regimens and investigate appropriate intravenous infusion times to reduce the risk of toxicity. Patients and methods: Once-daily busulfan dosing regimens for pediatric patient were reviewed and selected including EMA- and FDA-based once-daily dosing regimens. We generated busulfan PK data of virtual pediatric patients using a previously developed population PK model. PK profiles and proportion of patients achieving the referenced maximum concentration (Cmax) and exposure to busulfan were used to evaluate the appropriateness of both infusion time and dosing regimens. Results: Predicted PK profiles and exposure of busulfan showed relatively similar distributions for all once-daily dosing regimens. Most patients exceeded the referenced Cmax possibly associated with a high risk of VOD with all once-daily regimens when applied with 3 hours of infusion. Conclusion: While intravenous infusion of once-daily busulfan is typically administered over 3 hours, our findings emphasize the necessity of considering sufficient infusion times to ensure safe drug utilization and prevent toxicity, which will aid in optimal busulfan use in pediatric oncology.

Neonatal Serum Gentamicin Concentrations and Outcomes Following Maternal Once-Daily Gentamicin Dosing.

OBJECTIVE: This study evaluated newborn gentamicin serum concentrations after birth and the effects on the newborn after extended interval gentamicin dosing in peripartum mothers. METHODS: This was a single-center, retrospective chart review of neonates born to mothers that received peripartum once-daily gentamicin dosing of approximately 5 mg/kg within 12 hours of delivery. A gentamicin serum concentration was obtained immediately after birth in the newborn. The primary outcome was initial neonatal gentamicin serum concentration after birth. Several secondary outcomes were evaluated including nephrotoxicity and ototoxicity. A subgroup analysis comparing baseline demographics of mother-newborn dyads with birth neonatal serum concentrations of less than 2 mcg/mL versus 2 mcg/mL or greater was performed. RESULTS: A total of 32 mother-newborn dyads were included. Newborns had a median gestational age of 39.4 weeks and median birth weight of 3.4 kg. The mean initial gentamicin serum concentration was elevated at 3.1 ± 1.9 mcg/mL among all newborns. The median maternal dose based on actual body weight in newborns with gentamicin serum concentrations less than 2 mcg/mL was 3.5 (IQR, 3.3-4.8) mg/kg versus 4.8 (IQR, 4.3-5.2) mg/kg in those that had serum concentrations of 2 mcg/mL or greater (p = 0.025). All newborn gentamicin serum concentrations were less than 2 mcg/mL for maternal doses given less than 1 hour prior to delivery (n = 8). There were no significant differences in nephrotoxicity or ototoxicity. CONCLUSIONS: Peripartum once daily dosing of gentamicin administered between 1 to 12 hours of birth may lead to clinically significant serum concentrations in newborns.

Impact of single-nucleotide polymorphisms on tacrolimus pharmacokinetics in liver transplant patients after switching to once-daily dosing.

BACKGROUND: The effects of multidrug resistance-1 (MDR1), ABCC2, and P450 oxidoreductase (POR)*28 gene polymorphisms on tacrolimus metabolism following a switch to once-daily dosing have not been elucidated. We investigated the effects of recipient and donor CYP3A5, MDR1, ABCC2, and POR*28 polymorphisms on tacrolimus pharmacokinetics following a switch to once-daily tacrolimus dosing. METHODS: Eighty-seven liver transplant recipients who were switched from twice- to once-daily tacrolimus dosing following living-donor liver transplantation and 81 matched donors were genotyped for CYP3A5, MDR1 (1236C>T, 2677G>T/A, and 3435C>T), ABCC2 (-24C>T, 1249G>A, and 3972C>T), and POR*28. Tacrolimus dose-adjusted trough levels (C0/dose) before and after the switch were determined and calculated based on past medical records. Recipients were divided into two groups, one group constituted of 38 patients with a C0/dose decrease of less than 30% following conversion (group 1) and the other constituted of 49 patients with a C0/dose decrease of ≥ 30% (group 2). RESULTS: CYP3A5 *1/*3 and *3/*3 were more frequent in recipients in group 1 (60.5% vs. 36.8%), while CYP3A5 *1/*1 was more frequent in group 2 (59.2% vs. 32.7%) (p = 0.016). The proportions of donor ABCC2 1249G>A genotypes AA and AG were higher in group 2 than in group 1 (20.4% vs. 5.3%; p = 0.042). CONCLUSION: Recipient CYP3A5 polymorphism and donor ABCC2 1249G>A polymorphism affected tacrolimus pharmacokinetics following the switch to once-daily dosing. Dose adjustment to maintain therapeutic tacrolimus levels following the switch to once-daily dosing should be considered based on polymorphisms in both the recipient and donor.

Evaluation of the long-term safety and effectiveness of tadalafil once daily in Chinese men with erectile dysfunction: interim results of a multicenter, randomized, open-label trial.

Once-daily tadalafil administration has been well established; however, studies about tadalafil once-daily treatment in the Chinese population are lacking. In this phase 4, postmarketing study, we ascertained the long-term safety and effectiveness of tadalafil 2.5 mg and 5.0 mg once daily in Chinese men with erectile dysfunction (n = 635). The primary endpoint of the study was safety at 12 months as assessed by the proportion of patients experiencing at least one treatment-emergent adverse event (serious or nonserious). The secondary endpoints included safety and effectiveness, measured by the International Index of Erectile Function-Erectile Function (IIEF-EF) domain scores. Similar adverse events to the known safety profile of tadalafil, such as nasopharyngitis, upper respiratory tract infection, headache, and dizziness, were detected. No new cardiovascular safety concerns were observed. After 3 months of treatment, significant increases in IIEF-EF domain scores were detected for both 2.5-mg (least squares [LS] mean change: 6.3; 95% confidence interval [CI]: 5.4-7.1; P < 0.001) and 5.0-mg (LS mean change: 7.4; 95% CI: 6.8-7.9; P < 0.001) tadalafil doses, and significance was maintained up to 12 months. In addition, approximately 40% of patients regained normal erectile function (IIEF-EF ≥26) following 1 year of tadalafil once-daily treatment. The findings in this study provide evidence for the extended effectiveness and tolerability of tadalafil, demonstrating no new safety concerns, in a Chinese population and make once-daily tadalafil administration a viable option for improving sexual performance and satisfaction in Chinese men with erectile dysfunction.

Design of Phthalazinone Amide Histamine H1 Receptor Antagonists for Use in Rhinitis.

The synthesis of potent amide-containing phthalazinone H1 histamine receptor antagonists is described. Three analogues 3e, 3g, and 9g were equipotent with azelastine and were longer-acting in vitro. Amide 3g had low oral bioavailability, low brain-penetration, high metabolic clearance, and long duration of action in vivo, and it was suitable for once-daily dosing intranasally, with a predicted dose for humans of approximately 0.5 mg per day.

The challenge of curbing aminoglycoside resistance: can antimicrobial stewardship programs play a critical role?

INTRODUCTION: Aminoglycosides are useful antimicrobials, primarily for serious infections involving aerobic gram-negative pathogens. The inevitable increase in aminoglycoside resistance has led to calls for reducing levels of inappropriate aminoglycoside prescribing through the implementation of various antibiotic stewardship programs (ASPs). These programs mainly include restriction policies and aminoglycoside cycling. Although aminoglycoside resistance rates appear essential for measuring effectiveness of these interventions, most studies have focused on economic outcomes or clinical efficacy and toxicities. Areas covered: In the present study we estimated through a systematic literature review, the impact of early cycling studies and ASPs to aminoglycoside resistance rates for gram-negative pathogens. Expert commentary: Most ASPs support a positive association between aminoglycoside control policies and decrease of resistance rates. However, factors associated with aminoglycoside resistance are complex and multifactorial making it difficult to attribute resistance changes to a specific intervention. Optimized, high-dose, extended-interval aminoglycoside dosing and subsequent dosage monitoring by means of area under the curve and Cmax estimation, seem the most important strategies to improve clinical outcome, minimize toxicity and diminish resistance. The role of the clinical laboratory, using rapid and advanced assays and involved in pharmacodynamic target achievements, is also crucial to enable individualized or tailored aminoglycoside therapy. Future ASPs will need to combine high-quality epidemiological tools, novel diagnostic approaches and effective infection control measures.

Safety of intravenous tobramycin in combination with a variety of anti-pseudomonal antibiotics in children with cystic fibrosis.

OBJECTIVES: Previous studies have examined renal safety of once daily intravenous tobramycin in individuals with cystic fibrosis. This has been mainly in combination with ceftazidime in an adolescent or adult population. In this report, we describe our institutional experience of once daily intravenous tobramycin in combination with a variety of second anti-pseudomonal antibiotics in children with cystic fibrosis. METHODS: We present a retrospective review including children with cystic fibrosis, who were admitted for a pulmonary exacerbation from January 2009 to December 2011, and treated using intravenous tobramycin. A literature review of once daily intravenous aminoglycoside dosing in cystic fibrosis was performed to compare our results to existing literature. RESULTS: A total of 35 subjects were divided into once daily dosing (n = 20) versus multiple daily dosing (n = 15) groups. Mean age was 11.3 years (± 5.7) for the once daily dosing group and 13.1 years (± 4.4) for the multiple daily dosing group (p = 0.34). All subjects had normal baseline serum creatinine at admission (once daily dosing 0.49 ± 0.14 mg/dL vs multiple daily dosing 0.62 ± 0.23 mg/dL, p = 0.07). All subjects received intravenous tobramycin, and most received piperacillin-tazobactam as their second anti-pseudomonal antibiotic (once daily dosing 45% and multiple daily dosing 40%). There was no significant change in serum creatinine in either group during antibiotic treatment (once daily dosing 0.08 ± 0.12 mg/dL vs. multiple daily dosing 0.06 ± 0.10 mg/dL, p = 0.43). All subjects had significant improvement in lung function following intravenous antibiotic therapy. CONCLUSION: We show that both once daily dosing and multiple daily dosing of intravenous tobramycin in combination with a variety of second anti-pseudomonal antibiotics were safe in terms of nephrotoxicity in children with cystic fibrosis. These findings are important given existing literature mainly examines once daily tobramycin in combination with ceftazidime, a cephalosporin, and the majority of our patients were on tobramycin with piperacillin-tazobactam, an extended spectrum penicillin plus beta-lactam. This contributes new information not previously examined in a pediatric cystic fibrosis population.

Once daily high dose tigecycline - pharmacokinetic/pharmacodynamic based dosing for optimal clinical effectiveness: dosing matters, revisited.

INTRODUCTION: Tigecycline has emerged as first line therapy for serious systemic infections due to important pathogens (except P. aeruginosa and Proteus sp.), including multi-drug resistant (MDR) and Gram negative bacilli (GNB), including carbapenem resistant Enterobacteriae. Tigecycline has a 'low resistance potential,' is protective against C. difficile, and is often the only antibiotic effective against MDR GNB, e.g., Klebsiella sp. Areas covered: Standard dose tigecycline therapy has been used for intra-abdominal infections, complicated skin/skin structure infections (cSSSIs), and CAP. Clinical experience with once daily high dose tigecycline (HDT), i.e., 200 - 400 mg (IV) x 1, then 100 - 200 mg (IV) q24 h, is reviewed. Optimal tigecycline efficacy is dependent on PK/PD based dosing. Suboptimal outcomes have been due to inappropriate use or suboptimal dosing. Expert commentary: Tigecycline's spectrum against nearly all important pathogens (including MSSA/MRSA, VSE/VRE, B. fragilis, C. difficile, MDR and GNB) assures tigecycline a critical place in the antibiotic armamentarium. Dosed optimally, HDT can be a cornerstone of antibiotic stewardship programs in preventing C. difficile, treating MDR GNB pathogens, and in preventing resistance. Properly used and optimally dosed, once daily HDT should be considered preferred therapy for severe systemic infections and those due to MDR GNB pathogens.

Discovery of MK-8970: an acetal carbonate prodrug of raltegravir with enhanced colonic absorption.

Developing new antiretroviral therapies for HIV-1 infection with potential for less frequent dosing represents an important goal within drug discovery. Herein, we present the discovery of ethyl (1-((4-((4-fluorobenzyl)carbamoyl)-1-methyl-2-(2-(5-methyl- 1,3,4-oxadiazole-2-carboxamido)propan-2-yl)-6-oxo-1,6-dihydropyrimidin-5-yl)oxy)ethyl) carbonate (MK-8970), a highly optimized prodrug of raltegravir (Isentress). Raltegravir is a small molecule HIV integrase strand-transfer inhibitor approved for the treatment of HIV infection with twice-daily administration. Two classes of prodrugs were designed to have enhanced colonic absorption, and derivatives were evaluated in pharmacokinetic studies, both in vitro and in vivo in different species, ultimately leading to the identification of MK-8970 as a suitable candidate for development as an HIV therapeutic with the potential to require less frequent administration while maintaining the favorable efficacy, tolerability, and minimal drug-drug interaction profile of raltegravir.

Comparative efficacy of tadalafil once daily in men with erectile dysfunction who demonstrated previous partial responses to as-needed sildenafil, tadalafil, or vardenafil.

OBJECTIVE: Phosphodiesterase type-5 inhibitors (PDE5Is) are first-line therapies for erectile dysfunction (ED). Sildenafil (SIL) and vardenafil (VAR) are approved for as-needed (PRN) dosing; tadalafil (TAD) is approved for both PRN and once-a-day (OaD) dosing for ED. Recent evidence suggests that TAD-OaD may be effective as therapy in men with an incomplete response to PRN-PDE5I therapy. This study evaluated whether TAD-OaD provides similar efficacy in men with ED who had previously demonstrated a partial response to PRN-PDE5I therapy. RESEARCH DESIGN AND METHODS: In this randomized, double-blind, placebo-controlled trial, men with a ≥3 month ED history received SIL 100 mg, TAD 20 mg, or VAR 20 mg during a 4 week open-label lead-in period. Those with International Index of Erectile Function - Erectile Function (IIEF-EF) domain scores <26 following lead-in treatment completed a 4 week washout period, then randomized to TAD 2.5 mg up-titrated to 5 mg, TAD 5 mg, or placebo (PBO) OaD for 12 weeks. MAIN OUTCOME MEASURES obtained from patients treated with TAD-OaD were compared to PBO-treated patients. Additionally, results of treatment with TAD-OaD were compared to results obtained from 4 week PRN-PDE5I therapy to determine whether OaD and PRN regimens provided comparable efficacy. CLINICAL TRIAL REGISTRATION: NCT01130532. MAIN OUTCOME MEASURES: International Index of Erectile Function (IIEF) domain scores; Sexual Encounter Profile (SEP) questions 2-5. RESULTS: Endpoint data was obtained from 590 men (391 TAD; 199 PBO). RESULTS for all IIEF and SEP measures were significantly better for TAD-OaD (p < 0.001 for all) compared to PBO and were comparable to those observed during PRN-PDE5I treatment. TAD 2.5 mg and TAD 5 mg OaD therapy were safe and generally well tolerated. CONCLUSION: Tadalafil once daily is a viable alternative to as-needed PDE5I therapy in men with ED. Key limitations include the lack of a PRN PDE5I study group during the double-blind period, and that many more patients took tadalafil than sildenafil or vardenafil during the PRN period.

Dolutegravir: clinical efficacy and role in HIV therapy.

The human immunodeficiency virus type-1 (HIV-1) integrase enzyme has recently emerged as a primary alternative target to block viral replication, and integrase strand transfer inhibitors (INSTIs) are now considered an alternative 'third agent' class of antiretroviral (ARV) drugs. Dolutegravir is the first next-generation INSTI showing some novel and intriguing characteristics: it has a favorable pharmacokinetic profile with a prolonged intracellular halflife, rendering feasible a once daily dosing without the need for pharmacokinetic boosting. Secondly, it is largely metabolized via uridine diphosphate glucuronosyltransferase-1A1 with a minor component of cytochrome P450 isoforms, thus allowing a low grade of drug-drug interactions, so that its metabolic profile consents co-administration with the majority of the other ARV drugs without dose adjustments. Lastly, but no less important, virological studies have clearly demonstrated that dolutegravir has a significant activity against HIV-1 isolates showing raltegravir and/or elvitegravir associated resistance mutations. The attributes of once daily administration and the potential to treat INSTI-resistant viruses make dolutegravir an interesting and promising new agent in the treatment of both naïve and experienced HIV-1 subjects. In this review, the main concerns on dolutegravir efficacy are focused through the analysis of the currently available data from clinical studies in naïve and experienced patients, evaluating its possible place within the anti-HIV-1 drug armamentarium. The development of newer once daily, single tablet coformulations improved drug adherence and maximized the success of ARV therapy. Pharmacokinetic studies and dose-ranging trials suggested that dolutegravir is a good candidate for a single tablet regimen in one or more new coformulated pills that will be available in the near future.

Prescribing practices for intravenous aminoglycosides in UK cystic fibrosis clinics: a questionnaire survey.

BACKGROUND: Intravenous aminoglycoside antibiotics are widely used to treat pulmonary infection with Pseudomonas aeruginosa in individuals with cystic fibrosis (CF). Over the last decade evidence has accumulated showing that the choice of aminoglycoside and the dosing regimen may help reduce adverse effects such as nephrotoxicity. METHODS: We undertook an online survey to determine current practice in UK CF Centres. RESULTS: We received a response from 35/48 (73%) centres. A once daily regimen was used in 30/35 (86%) centres. Around one third had stopped using gentamicin in the last 10 years. In most cases respondents reported changing practice in response to new evidence or evidence based guidelines. Obstacles to introducing evidence based practice were identified both at the level of the CF Centre and the hospital trust. CONCLUSIONS: A once daily aminoglycoside regimen is now used in the majority of UK CF Centres. Tobramycin is first line and many centres have stopped using gentamicin. Obstacles to evidence based practice remain in a minority of centres.

Udenafil: efficacy and tolerability in the management of erectile dysfunction.

Udenafil is a potent novel phosphodiesterase-5 inhibitor approved for use in Korea. Udenafil has unique properties, with a T max of 1.0-1.5 h and a T 1/2 of 11-13 h (a relatively rapid onset and a long duration of action). Therefore, both on-demand and once-daily use of udenafil have been reported. Udenafil's efficacy and tolerability have been evaluated in several studies, and recent and continuing studies have demonstrated udenafil's promise in both dosing regimens. Presently, tadalafil is the only FDA-approved drug for daily dosing, but udenafil can be used as a once-daily dose for erectile dysfunction patients who cannot tolerate tadalafil due to phosphodiesterase subtype selectivity. Udenafil as an on-demand or once-daily dose is effective and tolerable, but more studies are needed in patients of other ethnicities and with comorbid conditions such as diabetes mellitus, hypertension, and benign prostate hyperplasia.

Mometasone furoate in the management of asthma: a review.

Inhaled corticosteroids (ICS) have proven to be the most effective and essential therapy for the treatment of bronchial asthma. The 2007 National Asthma Education and Prevention Program guidelines recommend ICS as preferred therapy for patients with mild to severe persistent asthma. Mometasone furoate (MF) is a relatively new ICS agent with high affinity for the glucocorticoid receptor. It is approved in the US for maintenance treatment of asthma for patients 4 years of age and older. It has been shown to be well tolerated with no significant adverse side effects observed in clinical trials and post-marketing surveillance. The efficacy of mometasone furoate has been established in large, well-designed studies. In patients with persistent asthma previously treated either with short-acting beta-agonists alone or twice-daily maintenance therapy with ICS, once-daily MF has been shown to be superior to placebo in improving lung function, symptom control, and quality of life; and has shown comparable efficacy compared with budesonide, beclomethasone, and fluticasone. Twice-daily dosing with MF has been demonstrated to successfully allow for reduction or elimination of oral corticosteroids in severe asthmatics.