Single Morning Dose Research Articles

Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials

Current guidelines to treat iron deficiency recommend daily provision of ferrous iron divided through the day to increase absorption. However, daily dosing and split dosing might increase serum hepcidin and decrease iron absorption from subsequent doses. Our study aim was to compare iron absorption from oral iron supplements given on consecutive versus alternate days and given as single morning doses versus twice-daily split dosing. We did two prospective, open-label, randomised controlled trials assessing iron absorption using (54Fe)-labelled, (57Fe)-labelled, or (58Fe)-labelled ferrous sulfate in iron-depleted (serum ferritin ≤25 μg/L) women aged 18-40 years recruited from ETH Zurich and the University of Zurich, Switzerland. In study 1, women were randomly assigned (1:1) to two groups. One group was given 60 mg iron at 0800 h (±1 h) on consecutive days for 14 days, and the other group was given the same doses on alternate days for 28 days. In study 2, women were assigned to two groups, stratified by serum ferritin so that two groups with similar iron statuses could be formed. One group was given 120 mg iron at 0800 h (±1 h) and the other was given the dose split into two divided doses of 60 mg at 0800 h (±1 h) and 1700 h (±1 h) for three consecutive days. 14 days after the final dose, the groups were each crossed over to the other regimen. Within-individual comparisons were done. The co-primary outcomes in both studies were iron bioavailability (total and fractional iron absorption), assessed by measuring the isotopic label abundance in erythrocytes 14 days after administration, and serum hepcidin. Group allocations in both studies were not masked and primary and safety analyses were done on an intention-to-treat basis. The studies were registered at ClinicalTrials.gov, numbers NCT02175888 (study 1) and NCT02177851 (study 2) and are complete. For study 1, 40 women were enrolled on Oct 15-29, 2015. 21 women were assigned to the consecutive-day group and 19 to the alternate-day group. At the end of treatment (14 days for the consecutive-day group and 28 days for the alternate-day group), geometric mean (-SD, +SD) cumulative fractional iron absorptions were 16·3% (9·3, 28·8) in the consecutive-day group versus 21·8% (13·7, 34·6) in the alternate-day group (p=0·0013), and cumulative total iron absorption was 131·0 mg (71·4, 240·5) versus 175·3 mg (110·3, 278·5; p=0·0010). During the first 14 days of supplementation in both groups, serum hepcidin was higher in the consecutive-day group than the alternate-day group (p=0·0031). In study 2, 20 women were enrolled between Aug 13 and 18, 2015. Ten women were assigned to receive once-daily dosing and ten were assigned to receive twice-daily divided dosing. No significant differences were seen in fractional (day 1-3 geometric mean: 11·8% [7·1, 19·4] once daily vs 13·1% [8·2, 20·7] twice daily; p=0·33) or total iron absorption (day 1-3: 44·3 mg [29·4, 66·7] once daily vs 49·4 [35·2, 69·4] twice daily; p=0·33) between the two dosing regimens. Twice-daily divided doses resulted in a higher serum hepcidin concentration than once-daily dosing (p=0·013). No grade 3 or 4 adverse events were reported in either study. In iron-depleted women, providing iron supplements daily as divided doses increases serum hepcidin and reduces iron absorption. Providing iron supplements on alternate days and in single doses optimises iron absorption and might be a preferable dosing regimen. These findings should be confirmed in iron-deficient anaemic patients. Swiss National Science Foundation, Bern, Switzerland.

A single dose of dapagliflozin, an SGLT-2 inhibitor, induces higher glycosuria in GCK- and HNF1A-MODY than in type 2 diabetes mellitus

AimsSGLT2 inhibitors are a new class of oral hypoglycemic agents used in type 2 diabetes (T2DM). Their effectiveness in maturity onset diabetes of the young (MODY) is unknown. We aimed to assess the response to a single dose of 10 mg dapagliflozin in patients with Hepatocyte Nuclear Factor 1 Alpha (HNF1A)-MODY, Glucokinase (GCK)-MODY, and type 2 diabetes.MethodsWe examined 14 HNF1A-MODY, 19 GCK-MODY, and 12 type 2 diabetes patients. All studied individuals received a single morning dose of 10 mg of dapagliflozin added to their current therapy of diabetes. To assess the response to dapagliflozin we analyzed change in urinary glucose to creatinine ratio and serum 1,5-Anhydroglucitol (1,5-AG) level.ResultsThere were only four patients with positive urine glucose before dapagliflozin administration (one with HNF1A-MODY, two with GCK-MODY, and one with T2DM), whereas after SGLT-2 inhibitor use, glycosuria occurred in all studied participants. Considerable changes in mean glucose to creatinine ratio after dapagliflozin administration were observed in all three groups (20.51 ± 12.08, 23.19 ± 8.10, and 9.84 ± 6.68 mmol/mmol for HNF1A-MODY, GCK-MODY, and T2DM, respectively, p < 0.001 for all comparisons). Post-hoc analysis revealed significant differences in mean glucose to creatinine ratio change between type 2 diabetes and each monogenic diabetes in response to dapagliflozin (p = 0.02, p = 0.003 for HNF1-A and GCK MODY, respectively), but not between the two MODY forms (p = 0.7231). Significant change in serum 1,5-AG was noticed only in T2DM and it was −6.57 ± 7.34 mg/ml (p = 0.04).ConclusionsA single dose of dapagliflozin, an SGLT-2 inhibitor, induces higher glycosuria in GCK- and HNF1A-MODY than in T2DM. Whether flozins are a valid therapeutic option in these forms of MODY requires long-term clinical studies.

Efficacy of mizoribine and prednisolone combination therapy in adult patients with IgA vasculitis.

Immunoglobulin (Ig)A vasculitis (IgAV), formerly known as Henoch-Schönlein purpura, is one of the most common vasculitis caused by an IgA-mediated immune complex. It occurs most frequently in childhood and less commonly in adulthood. As for the treatment of IgAV in adults, there are few studies dealing with the administration and efficacy of intravenous pulse steroid therapy or combination therapy using prednisolone (PSL) and immunosuppressive drugs. Mizoribine (MZB) is a newly developed immunosuppressive drug with few adverse effects; however, there are currently few studies using MZB in adult patients with IgAV. In this study, we evaluated the efficacy of MZB combined with a course of PSL in adult patients with IgAV. Five patients with adult onset IgAV were enrolled in the study. All patients received oral PSL (initial dose 30-50mg/day), and MZB was administered orally at a single morning dose of 150mg. We investigated the clinical manifestations and prognosis of these patients receiving the combination therapy of MZB and PSL retrospectively. All patients showed complete or partial remission of proteinuria and microscopic hematuria with the combination therapy of MZB and PSL. Furthermore, no significant adverse effects were observed. Although this study had an uncontrolled small group, our results indicate that the combination of MZB with PSL could be a possible new treatment for adult patients with IgAV.

Efficacy of Medical Expulsive Therapy in Renal Calculi Less than or Equal to 5 Millimetres in Size.

Natural history and modality of treatment for asymptomatic renal calculi less than or equal to 5 millimetres in size is still unknown. Many options are available ranging from medical expulsive therapy to minimally invasive surgery. Till date no study has focussed on this very common but asymptomatic issue. Hence, this study is undertaken to evaluate efficacy of medical expulsive therapy in renal calculi less than or equal to 5mm in size. A prospective, parallel group, randomized study was carried out from 1st June 2014 to 31st May 2015, with total of 100 patients, 50 patients in each group. Patients with renal stones less than or equal to 5mm were included in the study. Group A Patients were administered medical expulsive therapy which included tamsulosin 0.4 mg daily at night time, furosemide 20mg, spironolactone 50mg in a single morning dose, and syrup potassium magnesium citrate 20Meq per dose three times a day for 12 weeks while group B patients were given placebo. The primary outcome variable was number of patients achieving clearance of stone during 12-week treatment period in both groups. No statistically significant differences in age, gender, stone size, and calyceal stone location was found between the two treatment arms. A spontaneous stone expulsion rate of 50% (at 6 weeks) and 86 %( at 12 weeks) was noted in group A versus 28% (at 6 weeks) and 38 % (at 12 weeks) in group B. Less number of pain episodes and less analgesic medication was required in group A as compared to group B. Medical Expulsive therapy for 12 weeks significantly improves stone free rates in renal calyceal calculi less than or equal to 5mm.

Pragmatic approach to manage new oral anticoagulants in patients undergoing dental extractions: a prospective case-control study.

The aim of this study was to validate a standardized pragmatic approach to manage new oral anticoagulants (NOACs) in patients who undergo dental extractions. This prospective case-control study in patients undergoing dental extraction included 26 patients (mean age 76 years, 57% male) treated with dabigatran, rivaroxaban, or apixaban and 26 matched controls. Regardless of timing of extraction, drug regimen, or renal function, patients were instructed to skip only the dose on the morning of the procedure. A procedural bleeding score was recorded and early and delayed bleeding was assessed at day 1 and day 7. Bleeding events were compared with a prospectively matched control group not taking any antithrombotic drug. There was no difference in the procedural bleeding score or in early bleeding events (5 in both groups). However, delayed bleeding occurred more frequently in anticoagulated compared to non-anticoagulated patients (7 versus none, p=0.01). Skipping the morning dose of NOACs avoids excess bleeding during and early after the procedure. However, anticoagulated patients had an increased risk of delayed bleedings. Further study is needed to determine the optimal post-procedural management. This is the first prospective study for the management of patients on NOACs undergoing dental extraction. Our pragmatic approach, omitting only a single morning dose, can guide clinical practice. Both patients and physicians should be aware of the increased delayed bleeding risk.

Evaluation of clinical parameters related to methotrexate therapy in lichen planus

Background: For better management of lichen planus a clinical trial of oral methotrexate is necessary in ow· country. Objective: The objective of this study is to evaluate efficacy and safety ofmethotrexate therapy in the treatment of lichen planus.Methods: It was a prospective randomized controlled clinical trial conducted in the department of Dermatology and Venereology, BSMMU, Dhaka, from January 2009 to December 2010. Forty four patients of lichen planus were included in the study. Cases (group-A, n=23) were treated with methotrexate (10 mg) single morning dose and control (group-B, n=21) were treated with mini pulse betamethasone (5mg) single morning dose on 2 consecutive days during the period of 12 weeks. Results: Clinical parameters were measured by follow up clinical examination. Morphological lesion of lichen planus improved 95. 7% in group-A and only 28.6% improved in group-B. At the end of study 82.6% bad no complaints of itching in group-A and 100% had no complaints of itching in group-B. 16(69.6%) patients in group-A were completely cured clinically but 10(47.6%) in group-B. Anemia 3(14.2%) and edema 12(57.1 %) developed in group-B but none in group-A. In group-B, dyspepsia 15(71.4%), acne 10(47.6%),mooning face 8(38.1%), striae 8(38.1%) and hyper­trichosis 4(19.0%) developed but none in group-A lntermittenr diarrhoea, headache, nausea and fatigue complained in both groups of patients but the percentage of complaints was higher amog group-8 compared to group-A. Menstrual abnormality developed in group-B 5(71.4%) but none in group-A.Conclusion: The overall adverse effects were less in group-A than group-B. Therefore, methotrexate can be used as an alternative safer option for the treatment of lichen planus.

Riociguat (BAY 63-2521) and aspirin: a randomized, pharmacodynamic, and pharmacokinetic interaction study.

In preclinical studies, drugs that increase cyclic guanosine monophosphate levels have been shown to influence platelet function/aggregation; however, the effect of riociguat on human platelets is unclear. Aspirin, a platelet inhibitor, is likely to be given concomitantly in patients receiving riociguat. It is therefore important to establish clinically whether (1) riociguat affects platelet function and (2) aspirin and riociguat interact. This randomized, open-label, crossover study investigated potential pharmacodynamic and pharmacokinetic interactions between these drugs in healthy male volunteers (N = 18). There were 3 treatment regimens: a single morning dose of riociguat 2.5 mg, aspirin 500 mg on 2 consecutive mornings, and both treatments together, with riociguat given on the second morning. Fifteen participants were available for pharmacodynamic/pharmacokinetic analysis. There was no effect of riociguat alone on bleeding time, platelet aggregation, and serum thromboxane B2 levels. The effects of aspirin on these parameters were not influenced by concomitant administration of riociguat. The pharmacokinetic profile of riociguat showed interindividual variability, which was independent of aspirin coadministration. Six of 17 participants available for safety evaluation reported at least 1 treatment-emergent adverse event. All adverse events were of mild severity, apart from 1 report of moderate headache. No serious adverse events occurred. In conclusion, riociguat demonstrated no clinically relevant pharmacodynamic or pharmacokinetic interactions with aspirin at the doses used in this study in healthy men; coadministration of riociguat and aspirin should therefore not require any dose adjustment for either drug.

Effectiveness of Methotrexate in prednisolone and thalidomide resistant cases of Type 2 lepra reaction: report on three cases

Type 2 lepra reactions, and its cutaneous manifestation, Erythema Nodosum Leprosum (ENL) are an immune complex mediated systemic condition, often complicating the disease and/or its treatment in cases of the lepromatous spectrum of leprosy. Prednisolone and thalidomide are the mainstay for the treatment of Type 2 lepra reactions. According to the guidelines set out by the WHO and the National Leprosy Elimination Programme (NLEP) of India cases of Type 2 lepra reaction should be managed with prednisolone, cofazimine and thalidomide. NLEP guidelines suggest that prednisolone at 1 mg/kg body wt/day is given to start with as a single morning dose after breakfast, and after the reaction/inflammation is controlled, to taper the prednisolone by 10 mg fortnightly till the dose of 20 mg/day is reached. Thereafter prednisolone is tapered by 5 mg/day, fortnightly till withdrawal. Clofazimine is given with corticosteroids in every case, starting with 100 mgs three times a day, tapering to 100 mgs after every 12 weeks. It is recommended not to exceed clofazimine beyond 12 months. Thalidomide can be used in resistant cases of ENL under strict supervision in tertiary care centres only. During the years 2009 and 2010, thalidomide was made available to our department through the kind donation of the NGO Lepra Society, India. This thalidomide was used for prednisolone/clofazimine non-responsive patients of Type 2 lepra reaction. The thalidomide schedule that we followed was, to start 100 mgs three times a day, tapered fortnightly

Analysis on the securityof preoperative oral sugar salt solution ofpatients with laparoscopic gallbladder excision

Objective To evaluate the effect of the preoperative oral sugar salt solution on patients with laparoscopic gallbladder excision. Methods A total of 178 patients with laparoscopic gallbladder excision were divided into observation group and control group with 89 cases in each. The control group adopted routine fasting way before operation. The patients in the observation group were treated with 300 ml of the sugar salt solution at the 10 o'clock on the evening before surgery. After midnight, nothing by mouth was allowed, except a single morning dose of 200 ml of the corresponding solution.The morning drink was taken at 2h before surgery. Visual analog scales(VAS) were used to score 11 different preoperative discomfort variables.Operational clinical and surgical data were recorded, which included the blood pressure, heart rate, blood glucose levels. Results The control group at different time measured blood glucose, heart rate, systolic pressure and diastolic pressure were statistically different (F=5.609, 5.771, 15.780, 12.335, P 0.05). And blood glucose after 24h, the heart rate after 6h, blood pressure after 6h time compared with other time points statistically significant differences(P 0.05). On the morning before surgery, patients in the control group mainly unwell feeling nervous, hunger, thirst, fatigue, pain, VAS score were significantly increased than those in the observation group(P<0.05). Conclusions Drinking the sugar salt solution at the 10 o'clock on the evening before surgery and 2h before surgery does not affect anesthesia intubation.and not increase the risk of regurgitation and aspiration during or after surgery and alleviatenervous, hunger, thirst, fatigue, pain. Key words: Sugar salt-solution; Fasting for solids and liquid; Celioscope operation; Laparoscopic cholecystectomy; Perioperative period

SINGLE VERSUS DIVIDED-DOSE STEROIDS IN TREATMENT OF NEPHROTIC SYNDROME

Introduction: Oral corticosteroids form the cornerstone for management of most children with nephrotic syndrome. Prednisolone should be administered at a dose of 60 mg/m²/day (maximum daily dose, 80 mg) for 4-6 weeks. Daily therapy may be either given, as a single morning or divided doses. We aim by this study to compare the regimen of giving steroids in a single daily dose with that of giving them in three-divided doses, as regard the compliance, response to treatment, and occurrence of complications. Patients and methods: The study was conducted on 30 patients having presumed steroid-responsive minimal change nephrotic syndrome. 15 patients were given prednisolone in a single daily dose. The other 15 patients were given prednisolone in three divided doses. Results: There was no significant statistical differences between the two groups of patients as regard the duration of treatment before remession or complications of nephrotic syndrome. No complications related to steroids were observed in any of our patients. Conclusion: Prednisolone, as a single morning dose is as effective as divided doses for inducing remission with no higher risk of complications. As single-dose steroid therapy is likely to be associated with better drug compliance, we recommend it as the regimen of choice for treatment of nephrotic syndrome.

Observaciones respecto a las acciones terapéuticas y farmacológicas de la fluocortolona

Se ha efectuado en 30 pacientes un estudio clínico de los efectos terapéuticos y farmacológicos de la fluocortolona (Ultralan-(R) 1), nuevo esteroide sintético derivado de la corticosterona. Como tratamiento complementario de las drogas tuberculostáticas fue administrada a 18 enfermos con diversas formas clínicas de tuberculosis (pleuresía con derrame, meningitis, siembra miliar), en 6 pacientes con reacciones de hipersensibilidad, 2 con lupus eritematoso sistémico, 1 con dermotomiositis y 3 con leucemía. Se ha podido apreciar que la fluocortolona posee un buen efecto anti-inflamatorio con una relativa poca potencialidad de ocasionar la aparición de maniIestaciones secundarias. En el segundo día de administración, las determinaciones de 17-0HS y 17-KS urinarias mostraron que, a una dosis única matutina de 30 mgms., la fluocortolona tiene un efecto supresivo de la función suprarrenal algo menor que 2 mgms. de dexametasona, como son administrados en el test de Liddle. Al finalizar la tercera semana de un curso de 4 semanas de tratamiento, el valor promedio de los 17-0HS urinarios descendió hasta constituir un 20% del valor basal y 3 días después de la suspensión del mismo alcanzó a ser 66 %.

MP27-04 TAMSULOSIN AS AN EXPULSIVE THERAPY FOR STEINSTRASSE AFTER EXTRACORPOREAL SHOCK WAVE LITHOTRIPSY: A RANDOMIZED CONTROLLED STUDY

You have accessJournal of UrologyStone Disease: Therapy III1 Apr 2014MP27-04 TAMSULOSIN AS AN EXPULSIVE THERAPY FOR STEINSTRASSE AFTER EXTRACORPOREAL SHOCK WAVE LITHOTRIPSY: A RANDOMIZED CONTROLLED STUDY Essam ElDin Moursy, Wael Gamal, and Abdelmenem Abuzeid Essam ElDin MoursyEssam ElDin Moursy More articles by this author , Wael GamalWael Gamal More articles by this author , and Abdelmenem AbuzeidAbdelmenem Abuzeid More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.367AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Steinstrasse is a well-known complication following extracorporeal shockwave lithotripsy (ESWL). The objective of this study was to evaluate the efficacy of tamsulosin as a management of steinstrasse. METHODS 88 patients with unilateral steinstrasse were treated between January 2005 and December 2008. The patients were randomly allocated into two equal groups. There were no significant differences between groups for age, gender, stone location, stone length or stone fragment size (p > 0.05). Patients in group 1 (study group) received a single daily morning dose of tamsulosin (0.4 mg) for a maximum of 4 weeks, in addition to pain-relieving therapy. Patients in group 2 (control group) received only the pain relieving therapy. All patients were checked weekly with a plain X-ray of the urinary tract, urinary ultrasonography, urine analysis and serum creatinine. Pain episodes, day of spontaneous stone expulsion, total analgesic dosage and drug side effects were recorded. RESULTS Stone expulsion occurred in 32 of the 44 patients (72.7%) receiving tamsulosin and in 25 of the 44 patients (56.8%) in the control group. Patients receiving tamsulosin had a significantly higher stone expulsion rate (p = 0.017). There were no significant differences between groups for mean stone expulsion time or number of analgesics used. Twelve patients (27.3%) in the group receiving tamsulosin and 19 patients (43.3%) in the control group needed hospitalization; the group difference was statistically significant (p = 0.017). CONCLUSIONS When compared with no treatment, tamsulosin can significantly facilitate expulsion of retained ureteral stone fragments following ESWL. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e276 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Essam ElDin Moursy More articles by this author Wael Gamal More articles by this author Abdelmenem Abuzeid More articles by this author Expand All Advertisement Advertisement Loading ...

Effects of a protein‐rich drink or a standard meal on the pharmacokinetics of elvitegravir, cobicistat, emtricitabine and tenofovir in healthy Japanese male subjects: A randomized, three‐way crossover study

This study investigated the effects of ingested food types on the pharmacokinetics of elvitegravir, cobicistat, emtricitabine, and tenofovir as a single-tablet regimen (STR) in Japanese HIV-negative healthy subjects. In this open-label, randomized, three-way crossover study, the pharmacokinetic profiles of elvitegravir, cobicistat, emtricitabine, and tenofovir were evaluated when administered with a standard breakfast, under fasting conditions, or with a nutritional protein-rich drink. All subjects (N = 11) received a single morning dose of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (150/150/200/300 mg). Administration under fasting conditions resulted in decreases in the mean AUCinf of elvitegravir and tenofovir by 50% and 28%, respectively, relative to administration with a standard breakfast, whereas the bioavailabilities of elvitegravir and tenofovir were comparable when administered with a standard breakfast or a nutritional protein-rich drink. Under fasting conditions, it appears that the bioavailabilities of elvitegravir and tenofovir were not equivalent to those when they were administered with either type of food, although they were bioequivalent to each other under fed conditions. Cobicistat and emtricitabine were bioequivalent under all conditions. These findings suggest that elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate should be administered with food, and that the bioavailability of elvitegravir and tenofovir is not affected by the type of meal ingested.

Gender differences in pharmacokinetics and pharmacodynamics of zolpidem following sublingual administration

The effect of dose and gender on the pharmacokinetics (PK) and pharmacodynamics (PD) of zolpidem after administration of a buffered zolpidem sublingual tablet (ZST; Intermezzo®, Purdue Pharma L.P., Stamford, CT, USA) was evaluated in healthy non-elderly male and female volunteers. Subjects received a single morning dose of ZST (1.0, 1.75, and 3.5 mg) or placebo in a four-way crossover study. In male and female subjects zolpidem PK were linear, with area under the curve (AUC) proportional to dose, and apparent oral clearance and elimination half-life independent of dose. However, AUC averaged 40% to 50% higher in females than in males receiving the same dose. The gender effect was incompletely explained by body weight. In females, ZST produced PD changes consistent with benzodiazepine agonist effects, particularly at the 3.5-mg dose. For several PD variables, PD effects were significantly related to plasma zolpidem concentrations when data were aggregated across subjects. However, there was variability in response among individuals. In males, PD effects of zolpidem seldom differed from placebo regardless of plasma concentration. The findings confirm that zolpidem clearance is lower in females than in males. PD effects of zolpidem from ZST are greater in female subjects, due to a combination of higher plasma concentrations and greater intrinsic sensitivity.

Influence of food on pharmacokinetics of zolpidem from fast dissolving sublingual zolpidem tartrate tablets

Ingesting food can impact the pharmacokinetics of sedative-hypnotic drugs. A buffered zolpidem sublingual tablet (ZST) recently became available for the treatment of middle-of-the-night awakening. In this randomized, open-label, single-site study, the pharmacokinetic profile of ZST was evaluated when administered while fasting and following a standard high-fat meal (fed state). Healthy adults aged 18-64 years received a single morning dose of 3.5 mg ZST in the fed or fasting state. From 20 min to 3 h post-dose, zolpidem plasma levels were lower in the fed state compared to the fasting state. After 4 h post-dose (corresponding to "morning wake time"), higher zolpidem plasma levels were evident in the fed state. Area under the concentration-time curve (AUC) values for the 0-8 h interval were 160 ng/mL h in the fed state and 203 ng/mL h in the fasting state (P < .001). In the fed versus fasting states, Cmax was 32.0 ng/mL versus 57.3 ng/mL (P < .001), respectively, and Tmax was 3.0 h versus 0.92 h (P < .001), respectively. Together these data suggest that administration of ZST in the fed state is not optimal for maximizing the likelihood of therapeutic benefit and minimizing the probability of residual sedation.

Switching to evening antihypertensive drug dosing improves nighttime blood pressure and dipping status in non-sleepy patients with obstructive sleep apnea

Purpose: Patients with Obstructive Sleep Apnea (OSA) are often hypertensive, and Continuous Positive Airway Pressure (CPAP) may improve at least the circadian profile of blood pressure (BP). As asymptomatic patients with OSA often refuse to follow CPAP treatment, we investigated the efficacy of antihypertensive drug chronotherapy on BP management in this setting. Methods: In a cross-over trial, we studied 40 patients (aged 52±9 years, 77% males) with newly diagnosed hypertension and never treated, at least moderate OSA (apnea-hypopnea index-AHI: 37±20/hour), without daytime sleepiness (Epworth Score ≤10 points). Patients were first applied treatment with valsartan (± amlodipine) in a single morning dose for 8-weeks. In a second period of 8-weeks, patients were assigned to receive the same regimen in a single evening dose before bedtime. Office and ambulatory BP were measured at baseline and after each treatment phase. Based on concurrent start of CPAP application, patients were divided into two groups: on-CPAP (n=19) and off-CPAP (n=21). Results: Office BP was significantly reduced at the end of both the morning and evening dose phases compared to baseline (by 19.5±11.0/15.0±8.6 mmHg and 23.1±11/16.5±8.4 mmHg, repeated measures ANOVA p<0.001). Evening dosing was accompanied by a significant further decrease of office systolic BP (by 3.6±6.5 mmHg, p=0.001) and diastolic BP (by 1.5±4.6 mmHg, p=0.043), compared to morning dosing. The decrease in 24-hour BP was significant but similar in the two dosing times (by 15.7±10.1/10.3±6.2 mmHg and 17.6±9.9/11.3±5.9 mmHg, p<0.001). However, evening compared to morning dosing caused a further reduction in nighttime BP by 4.2±8.4/2.87±5.9 mmHg (p=0.003 and 0.004 respectively). Prevalence of nighttime dipping increased from 32.5% at baseline modestly to 40% with the morning dose and significantly to 62.5% with the evening dose (p=0.001). Split-plot ANOVA revealed that changes in office, ambulatory and nighttime BP were similar between the on- and off-CPAP groups. Conclusions: Evening dosing of antihypertensive treatment effectively improves BP levels and dipping status in non-sleepy patients with OSA, irrespective of application of CPAP.

Switching therapy to bedtime for uncontrolled hypertension with a nondipping pattern

Uncontrolled hypertension is present in most patients treated with only a single morning dose or fixed dose drug combination; usually a third of them have a high prevalence of a nondipper blood pressure pattern, especially patients with chronic illness. In most cases, nondipping is related partly to the absence of 24-h therapeutic coverage of the single morning doses. We have investigated the usefulness of shifting therapy to evening instead of the morning. The aim of the study was to better control blood pressure and convert patients with a nondipping pattern to a dipper pattern without the need to increase the dose of their drugs or the addition of any other family of drugs. Among 200 hypertensive patients, we investigated the impact of treatment time on the blood pressure pattern in 60 patients (33.3%) with uncontrolled hypertension with a nondipper pattern on the basis of clinic measurements who were studied by 24-h ambulatory monitoring during 2 and 4 months of follow-up; all of them received their treatment in the morning. This group of patients was divided randomly into two groups of 30 patients each; one group continued to receive the medication on awakening and the other took their medication at bedtime. Most of the treatment involved calcium channel blockers and other angiotensin-converting-enzyme inhibitors (ACEI), and 20 patients were taking one tablet of combined treatment (calcium blocker with ACEI). The percentage of patients with controlled ambulatory blood pressure was 0.86 among patients taking the drug at bedtime (P=0.005). Twenty-six patients with uncontrolled hypertension, receiving one drug or combined therapy at bedtime, showed a significant reduction in the 24-h mean systolic and diastolic blood pressure (6.2 and 2.6 mmHg, respectively; P<0.009). This reduction was more prominent during night-time (8.3 and 5.0 mmHg; P<0.001). In addition, all 26 patients showed normal blood pressure less than 140/90 during clinic measurement at daytime. Only four patients treated with monotherapy in the morning were unresponsive to the switching, and their blood pressure was controlled by the addition of a second drug at bedtime. The control group (who continued taking therapy in the morning) showed no reduction in blood pressure during night-time and remained with uncontrolled hypertension as they were at the beginning of the study. In patients with uncontrolled hypertension, switching of therapy to bedtime should be considered to improve control and to avoid the nondipper pattern before any attempt is made to increase the dose or add more drugs. We need other research studies with long time follow-up to verify the efficacy of switching therapy.

Adverse outcome of methotrexate and mini pulse betamethasone in the treatment of lichen planus

The objectives of this study were to compare the adverse outcome of methotrexate and mini pulse betamethasone therapy in the treatment of lichen planus. It was a clinical trial conducted in the department of Dermatology and Venereology, Bangabandhu Sheikh Mujib Medical University, Dhaka, from January 2009 to December 2010. Forty four patients of lichen planus were included in the study. Patients in Group-A, (n = 23) were treated with methotrexate (10 mg) single morning dose and group-B (n = 21) were treated with mini pulse betamethasone (5 mg) single morning dose on 2 consecutive days during the period of 12 weeks. Adverse outcomes were measured by clinical examination and laboratory investigations during follow up visits. Anemia 3 (14.2%) and edema 12 (57.1%) developed in group-B but none in group-A. In group-B, dyspepsia 15 (71.4%), acne 10 (47.6%), mooning face 8 (38.1%), striae 8 (38.1%) and hypertrichosis 4 (19.0%) developed but none in group-A. Intermittent diarrhoea, headache, nausea and fatigue complained in both groups of patients but the percentage of complaints was higher among group-B compared to group-A. Menstrual abnormality developed in group-B 5(71.4%) but none in group-A. Laboratory investigations showed abnormality in platelet count and SGPT in group-A but none in group-B. The adverse effects of methotrexate on haematological parameter and liver functions were mild and could be prevented by reducing the dose but the adverse effects of betamethasone were unavoidable. The overall adverse effects were less in group-A than group-B. Therefore, methotrexate can be used as an alternative safer option for the treatment of lichen planus.

Efficacy of lisdexamfetamine dimesylate throughout the day in children and adolescents with attention-deficit/hyperactivity disorder: results from a randomized, controlled trial

Lisdexamfetamine dimesylate (LDX) is a long-acting, prodrug stimulant therapy for patients with attention-deficit/hyperactivity disorder (ADHD). This randomized placebo-controlled trial of an optimized daily dose of LDX (30, 50 or 70 mg) was conducted in children and adolescents (aged 6–17 years) with ADHD. To evaluate the efficacy of LDX throughout the day, symptoms and behaviors of ADHD were evaluated using an abbreviated version of the Conners’ Parent Rating Scale-Revised (CPRS-R) at 1000, 1400 and 1800 hours following early morning dosing (0700 hours). Osmotic-release oral system methylphenidate (OROS-MPH) was included as a reference treatment, but the study was not designed to support a statistical comparison between LDX and OROS-MPH. The full analysis set comprised 317 patients (LDX, n = 104; placebo, n = 106; OROS-MPH, n = 107). At baseline, CPRS-R total scores were similar across treatment groups. At endpoint, differences (active treatment − placebo) in least squares (LS) mean change from baseline CPRS-R total scores were statistically significant (P < 0.001) throughout the day for LDX (effect sizes: 1000 hours, 1.42; 1400 hours, 1.41; 1800 hours, 1.30) and OROS-MPH (effect sizes: 1000 hours, 1.04; 1400 hours, 0.98; 1800 hours, 0.92). Differences in LS mean change from baseline to endpoint were statistically significant (P < 0.001) for both active treatments in all four subscales of the CPRS-R (ADHD index, oppositional, hyperactivity and cognitive). In conclusion, improvements relative to placebo in ADHD-related symptoms and behaviors in children and adolescents receiving a single morning dose of LDX or OROS-MPH were maintained throughout the day and were ongoing at the last measurement in the evening (1800 hours).

Safety, tolerability and pharmacokinetics of repeat dosing of the antibiotic GSK1322322, a peptide deformylase inhibitor: a randomized placebo-controlled study

GSK1322322 is a potent inhibitor of peptide deformylase, an essential bacterial enzyme required for protein maturation. In this two-part, double-blind, randomized, placebo-controlled, Phase 1 study (study identifier: PDF112668), the safety, tolerability and pharmacokinetics of single and repeat oral-dose GSK1322322 (500-1500 mg) in healthy adult and elderly volunteers were evaluated. Part A included GSK1322322 doses of 500, 750, 1000 and 1500 mg in healthy adults; Part B evaluated 1000 mg of GSK1322322 in healthy elderly volunteers. Volunteers received a single morning dose of a powder-in-bottle formulation of GSK1322322 or placebo on day 1, no dosing on day 2 and twice-daily dosing on days 3-12. Of 52 enrolled volunteers, 40 and 12 volunteers were treated with GSK1322322 and placebo, respectively. Mean plasma GSK1322322 trough concentration increased with increasing dose and reached steady-state after 2 days of repeat dosing. After single dosing of GSK1322322, maximum plasma concentration and exposure (AUC) were dose proportional from 500 to 1500 mg. However, after repeat dosing, AUC values at steady-state increased slightly more than proportionally, possibly because of a slightly longer terminal elimination t&frac12; after repeat dosing (compared with single-dose t&frac12;) at higher doses (1000 and 1500 mg). There was no age effect or diurnal variation in the GSK1322322 pharmacokinetic profile. GSK1322322 was generally well tolerated-all adverse events were mild to moderate in intensity. Repeat oral GSK1322322 (500-1500 mg) for 10 days was well tolerated. These data warrant further clinical investigation of GSK1322322.