Effect of Rivastigmine on Mobility of Patients with Higher-Level Gait Disorder: A Pilot Exploratory Study

Background

Higher-level gait disorder (HLGD) in older adults is characterized by postural instability, stepping dysrhythmicity, recurrent falls and progressive immobility. Cognitive impairments are frequently associated with HLGD.

Objectives

The aim of this study was to compare gait and cognitive performance before and after the use of rivastigmine in patients with HLGD, free from cognitive impairment or Parkinsonism.

Methods

Fifteen non-demented patients with HLGD (age 79.2 ± 5.9 years; 11 women; Mini-Mental State Examination [MMSE] 28.3 ± 1.4) received escalating doses of rivastigmine for 12 weeks in an open-label, pilot study. They were assessed before and after treatment (week 0 and week 12), and after a 4-week washout period (week 16). Assessments included the Mindstreams computerized neuropsychological battery, Activities-specific Balance Confidence Scale, State-Trait Anxiety Inventory, Geriatric Depression Scale, Timed Up and Go (TUG) test, gait speed and stride time variability. One-way multiple analysis of variance tests for repeated measures were used, and Pillai’s trace test was considered as robust to investigate significant differences.

Results

The mean dose of rivastigmine during the 8–12 week period was 5.1 ± 2.3 mg/day. A positive effect was observed on the Mindstreams memory subscale and anxiety scores [Pillai’s trace: F(6,724) = 0.508, p = 0.010; and F(7,792) = 0.545, p = 0.006, respectively, over the course of the study] as well as on mobility (TUG test) [Pillai’s trace: F(4,863) = 0.448; p = 0.028], whereas gait speed and stride time variability did not change.

Conclusions

The use of relatively low-dose rivastigmine did not affect gait speed and stride time variability; however, the general mobility and anxiety were improved. These preliminary results warrant a larger, randomized, placebo-controlled study.     

Intravitreal pegaptanib sodium (Macugen?) for treatment of diabetic macular oedema: a morphologic and functional study

AIMS

To study whether morphologic (foveal thickness, FT) variations of clinically significant macular oedema (CMO) in patients suffering from diabetes following intravitreal pegaptanib sodium (IVP) injection were associated with functional [macular sensitivity (MS) and colour discrimination (CD)] changes.

METHODS

A longitudinal, interventional, non-randomized study was performed. FT was assessed by optical coherence tomography (OCT), MS by microperimetry, best-corrected visual acuity (BCVA) by early treatment diabetic retinopathy study charts (ETDRS) and CD by Farnswoth-Munsell test. The treatment protocol consisted of three consecutive injections (0.3 mg/0.05 ml; baseline, week 6 and week 12). Follow-up checks were scheduled at 18, 24, 36 and 48 weeks, after injections.

RESULTS

Thirty eyes of 30 patients with clinically significant CMO were included for analysis. After IVP a significant decrease of FT occurred with a mean reduction from baseline of 56.9% (P= 0.0001). An improvement of functional parameters was recorded in all patients (BCVA from 18.2 ± 8.5 letters to 25.5 ± 8.4 letters, P < 0.005, MS from 8.6 ± 2.16 dB to 10.6 ± 2.61 dB, P < 0.001, colour analysis from 376.1 ± 125.6 TES to 116 ± 34.6 TES, P= 0.0001). A statistically significant correlation between FT and BCVA as well as MS and CD was also found. Neither ocular nor systemic adverse events were reported.

CONCLUSIONS

Intravitreal pegaptanib significantly reduced FT, with a concomitant improvement of MS and CD. This association emphasizes the efficacy of IVP in the treatment of CMO.     

Pharmacokinetics of Coadministered Guanfacine Extended Release and Lisdexamfetamine Dimesylate

Background

In clinical practice, α₂-adrenoceptor agonists have been adjunctively administered with psychostimulants for the treatment of attention-deficit/hyperactivity disorder (ADHD). Two studies have examined the adjunctive use of guanfacine extended release (GXR, Intuniv^®; Shire Development LLC, Wayne, PA, USA) with psychostimulants in children and adolescents with a suboptimal response to psychostimulant treatment. However, the potential for pharmacokinetic drug–drug interactions (DDIs) between GXR and lisdexamfetamine dimesylate (LDX, Vyvanse^®; Shire US LLC, Wayne, PA, USA) has not been thoroughly evaluated.

Objective

The primary objective of this study was to examine the pharmacokinetics of GXR 4 mg and LDX 50 mg given as single doses alone and in combination.

Study Design

This was an open-label, randomized, three-period crossover, DDI study.

Setting

The study was conducted in a single clinical research center.

Participants

Forty-two healthy adults were randomized in this study.

Interventions

Subjects were administered single oral doses of GXR 4 mg, LDX 50 mg, or GXR and LDX in combination.

Main Outcome Measures

Blood samples collected predose and up to 72 h postdose assessed guanfacine, LDX, and d-amphetamine levels. Bioequivalence was defined as the 90 % confidence intervals (CIs) of the geometric mean ratios of the area under the plasma concentration–time curve extrapolated to infinity (AUC_0–∞) and maximum plasma concentration (C_max) falling within the bioequivalence reference interval (0.80–1.25). Safety measures included adverse events, vital signs, and electrocardiograms (ECGs).

Results

Forty subjects completed the study. Following administration of LDX alone or in combination with GXR, the statistical comparisons of the AUC_0–∞ and C_max of d-amphetamine fell entirely within the reference interval. For guanfacine, the 90 % CI of the geometric mean ratio of AUC_∞ for the two treatments was within the bioequivalence criteria, but for C_max the upper bound of the 90 % CI exceeded the standard range for bioequivalence by 7 %. This relatively small change is unlikely to be clinically meaningful. Treatment-emergent adverse events (TEAEs) were reported by 42.9 % of subjects; the most commonly reported TEAEs included dizziness (5.0, 7.3, and 7.3 %) and headache (7.5, 4.9, and 7.3 %) following administration of GXR, LDX, and GXR and LDX in combination, respectively. Clinically significant ECG abnormalities occurred in one subject following administration of LDX and in one subject following coadministration of GXR and LDX.

Conclusions

In healthy adults, coadministration of GXR and LDX did not result in a clinically meaningful pharmacokinetic DDI compared with either treatment alone. No unique TEAEs were observed with coadministration of GXR and LDX compared with either treatment alone.     

Investigation of the Hemostatic Effect of a Transdermal Patch Containing 0.55?mg Ethinyl Estradiol and 2.1?mg Gestodene Compared with a Monophasic Oral Contraceptive Containing 0.03?mg Ethinyl Estradiol and 0.15?mg Levonorgestrel: An Open-Label,Randomized, Crossover Study

Background

Transdermal delivery of contraceptives offers several advantages over combined oral contraceptives (COCs), including effective absorption and the provision of relatively constant serum concentrations. Ethinyl estradiol (EE) and the progestin gestodene are well-absorbed through the skin and, therefore, well-suited for use in a transdermal contraceptive patch.

Objective

The objective of this study was to investigate the impact of a once-weekly transparent, transdermal patch delivering low doses of EE and gestodene equivalent to a COC containing 0.02 mg EE and 0.06 mg gestodene on hemostasis parameters compared with a monophasic COC containing 0.03 mg EE and 0.15 mg levonorgestrel.

Methods

In this single-center, open-label, randomized, crossover study, 30 women (aged 18–35 years) received three cycles of each treatment, separated by a two-cycle washout period. The primary outcome measure was the absolute change from baseline in prothrombin fragments 1 + 2 and d-dimer.

Results

For both treatments, prothrombin fragments 1 + 2 remained stable during the first treatment period, and increased only slightly in the second period (mean absolute change 0.025 and 0.028 nmol/L in the novel Bayer patch and COC groups, respectively). Increases in d-dimer were observed in both periods (mean absolute change 107.0 ± 147.2 ng/L for the novel Bayer patch and 113.7 ± 159.0 ng/L for the COC). There were no statistically significant treatment differences in prothrombin 1 + 2 or d-dimer (p = 0.667 and p = 0.884, respectively) and no statistically significant treatment sequence or period effects.

Conclusion

A COC containing 0.03 mg EE and 0.15 mg levonorgestrel and the novel Bayer patch have comparable influence on hemostatic endpoints. Both treatments were well-tolerated by subjects.     

Serum Concentration of Lignocaine After Pertubation: An Observational Study

Objective

The objective of this study was to report the serum concentration of lignocaine after pertubation in patients with endometriosis.

Design

Prospective observational study.

Setting

The study was carried out at a gynaecological outpatient unit in Stockholm, Sweden.

Population

Eligible patients had endometriosis with a dysmenorrhoic pain score of >50 mm on a visual analogue scale, and patent fallopian tubes.

Methods

Patients with endometriosis (n = 25) were included in the study. The patients received pre-ovulatory pertubations with lignocaine hydrochloride 10 mg (n = 16) or ringer acetate (placebo, n = 9). The procedure comprised passing the study solution through the uterus and the fallopian tubes via an intra-cervical balloon catheter. Serum samples were collected at 0, 5, 15 and 30 min after pertubation.

Main Outcome Measures

The serum samples were analysed for the concentration of lignocaine with an LCMS-SIM method.

Results

Low levels of lignocaine were detected in the serum samples following pertubation of 10 mg lignocaine hydrochloride. The highest observed concentration was seen after 30 min (mean 0.050 μg/ml), with an individual maximum of 0.124 μg/ml. Maximum concentration (C_max) and time to C_max (T_max) could not be calculated, since the highest values were observed in the 30-min samples, which was the last sample obtained. Lignocaine was not detected after pertubation with placebo.

Conclusions

The serum levels of lignocaine following pertubation of 10 mg lignocaine hydrochloride are detectable but low. Lignocaine pertubated through the fallopian tubes reaches the peritoneal cavity and diffuses through the peritoneum into the blood circulation. Pertubation with lignocaine is safe and has no lignocaine-related adverse events.     

Pharmacokinetics of Coadministration of Guanfacine Extended Release and Methylphenidate Extended Release

Background

α₂-Adrenoceptor agonists are used adjunctively to psychostimulants in treating attention-deficit/hyperactivity disorder (ADHD) when psychostimulants alone do not sufficiently reduce symptoms. However, data on the pharmacokinetic profiles and safety of combination treatments in ADHD are needed.

Objective

The primary objective of this study was to evaluate the pharmacokinetic profiles of guanfacine extended release (GXR) and methylphenidate hydrochloride (MPH) extended release, alone and in combination.

Study Design

This was an open-label, randomized, three-period crossover, drug–drug interaction study.

Setting

The study was conducted at a single clinical research center.

Participants

Thirty-eight healthy adults were randomized in this study.

Interventions

Subjects were administered single oral doses of GXR (Intuniv^®; Shire Development LLC, Wayne, PA, USA) 4 mg, MPH (Concerta^®; McNeil Pediatrics, Titusville, NJ, USA) 36 mg, or GXR and MPH combined.

Main Outcome Measures

Guanfacine, dexmethylphenidate (d-MPH), and l-methylphenidate (l-MPH) levels were measured with blood samples collected predose and up to 72 h postdose. Safety evaluations included treatment-emergent adverse events (TEAEs), vital signs, and electrocardiograms (ECGs).

Results

Thirty-five subjects completed the study. Analyses of the 90 % confidence intervals (CIs) for the geometric mean ratios of the maximum plasma concentration (C_max) and area under the concentration–time curve extrapolated to infinity (AUC_∞) values for guanfacine and d-MPH following administration of GXR or MPH alone or combined met strict bioequivalence criteria (90 % CIs within the interval of 0.80–1.25). Overall, combining GXR and MPH did not alter the pharmacokinetic parameters of either medication. Sixteen subjects (42.1 %) had at least one TEAE. The most commonly reported TEAEs included headache and dizziness following GXR, MPH, and GXR and MPH combined. Two subjects had clinically significant abnormalities in ECG results following coadministration: both events were mild and resolved the same day.

Conclusions

In this short-term, open-label study of healthy adults, coadministration of GXR and MPH did not result in significant pharmacokinetic drug–drug interactions. No unique TEAEs were observed with coadministration of GXR and MPH compared with either treatment alone.     

Inhaler Competence and Patient Satisfaction with Easyhaler?: Results of Two Real-Life Multicentre Studies in Asthma and COPD

Objective

The aim of this study was to investigate patients’ inhaler competence and satisfaction with the Easyhaler^® dry powder inhaler.

Design

Two open, uncontrolled, non-randomised studies.

Setting

Real life based on patients attending 56 respiratory clinics in Hungary.

Participants

Patients with asthma or chronic obstructive pulmonary disease (COPD) (n = 1016).

Intervention

In a 3-month study, adult patients (age range 18–88 years; n = 797) received twice-daily inhalations of formoterol via Easyhaler^®, and in a consequential study (from one visit to another, with 3–12 months in-between) children and adolescents (age range 4–17 years; n = 219) received salbutamol via Easyhaler^® as needed.

Main Outcome Measures

Control of six Easyhaler^® handling steps and patients’ satisfaction with Easyhaler^® based on questionnaires.

Results

Correct performances (minimum and maximum of the six steps) were noticed after one demonstration in 92–98 % of the adults, 87–99 % of the elderly, 81–96 % of the children and 83–99 % of the adolescents. These figures had markedly increased at the last visit. Repeat instructions were necessary in 26 % of the cases. Investigators found Easyhaler^® easy to teach in 87 % of the patients and difficult in only 0.5 %. Patients found Easyhaler^® easy to learn and use, and the patients’ (and parents’) satisfaction with the inhaler was very high. Lung function values [forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC), peak expiratory flow (PEF)] improved statistically significantly during the studies, indicating good inhaler competence and treatment adherence.

Conclusion

Investigators found Easyhaler^® easy to teach and patients found it easy to use, and their satisfaction with the device was high.     

α-Lipoic Acid and Superoxide Dismutase in the Management of Chronic Neck Pain: A Prospective Randomized Study

Background and Objective

Since oxidative stress plays a pathogenetic role in chronic neck pain (CNP), we investigated whether a combination of α-lipoic acid (ALA) and superoxide dismutase (SOD) might improve pain control and the efficacy of physiotherapy (“multimodal therapy”) in patients with CNP.

Setting

This study was conducted in the Rehabilitation Unit of the Department of Surgical and Oncological Sciences at the University Policlinic in Palermo, Italy.

Design and Patients

This was a prospective, randomized, open study in outpatients.

Intervention

Patients randomly received either physiotherapy alone (group 2; n = 45) or a combination of ALA 600 mg and SOD 140 IU daily in addition to physiotherapy (group 1; n = 51), for 60 days. Pain was assessed by a visual analogue scale (VAS) and a modified Neck Pain Questionnaire (mNPQ). Treatment compliance and safety were also evaluated.

Results

Both groups experienced a significant reduction in the VAS and mNPQ scores after 1 month; however, while no further improvement was observed in group 2 at 60 days, group 1 showed a further VAS reduction (p < 0.001). In addition, in the mNPQ at 60 days, more patients in group 1 than in group 2 reported that their neck pain was improved (p < 0.01), and they showed greater compliance with prescribed physiotherapy (p = 0.048). No drug reaction was observed.

Conclusion

Use of ALA/SOD in combination with physiotherapy may be a useful approach to CNP, being antioxidants that act on nerve inflammation and disease progression.

Clinical Rehabilitation Impact

These preliminary observations suggest that some interesting goals (better pain control and physical wellbeing) can be achieved by multimodal therapy in CNP patients.     

A Multicenter,Open-Label Study of an Intravenous Short-Acting β1-Adrenergic Receptor Antagonist Landiolol Hydrochloride for Coronary Computed Tomography Angiography by 16-Slice Multi-Detector Computed Tomography in Japanese Patients with Suspected Ischemic Cardiac Disease

Background

During coronary computed tomography (CT) angiography (CCTA), β-blockers (β-adrenergic receptor antagonists) have commonly been used to lower heart rate and improve image quality.

Objectives

The aim of this study was to investigate the image quality-improving effect as well as the heart rate-lowering effect of landiolol hydrochloride (an intravenous short-acting β₁-adrenergic receptor antagonist) in CCTA by 16-slice multi-detector CT (MDCT).

Methods

A total of 39 subjects suspected of having ischemic cardiac disease and requiring CCTA received 0.125 mg/kg of landiolol hydrochloride to study the efficacy and safety of landiolol hydrochloride in a multicenter open-label clinical study. The endpoint was the diagnosable proportion (proportion of subjects whose coronary stenosis was diagnosable).

Results

The diagnosable proportions for the reconstruction images at mid-diastole were 56.0 %. The diagnosable proportions for the optimal reconstruction images were 65.4 %. The mean heart rate-lowering effect was observed soon after administration of landiolol hydrochloride; the peak of the effect was reached in 3–5 min, and the effect wore off in 30 min after completion of administration. The mean heart rate-lowering proportion at that time was −14.46 ± 8.4 %.

Conclusions

Landiolol hydrochloride was confirmed to reduce heart rate significantly and rapidly after intravenous injection and this suggests that the study drug is a safe and useful agent for improving the image quality of CCTA by 16-slice MDCT.     

An In Vitro Analysis of Disintegration Times of Different Formulations of Olanzapine Orodispersible Tablet: A Preliminary Report

Background

Orodispersible tablets (ODTs) are tablet or wafer forms of medication that disintegrate in the mouth, aided only by saliva. ODTs rely on different fast dissolve/disintegration manufacturing technologies.

Objectives

Disintegration time differences for several olanzapine ODT forms were investigated. Risperdal M-Tab^® was included as a non-olanzapine ODT comparator.

Research Design and Methods

Eleven olanzapine ODT examples and orodispersible risperidone strengths were evaluated in vitro for formulation composition, manufacturing method, disintegration and dissolution characteristics, and formulation differences in comparison with freeze dried Zydis^® ODT. Automated dissolution test equipment captured ODT dissolution rates by measuring real-time release of active ingredient. A high-speed video camera was used to capture tablet disintegration times in warm simulated saliva.

Main Outcome Measure

The main outcome measure was the disintegration and dissolution characteristics of the ODT formulations.

Results

The ODT manufacturing method was associated with time to disintegrate; the fastest were freeze dried tablets, followed by soft compressed tablets and then hard/dense tablets. Olanzapine Zydis^® was the only ODT that completely disintegrated in less than 4 s for all strengths (5, 10, 15, and 20 mg), followed by 5-mg Prolanz FAST^® (12 s) and then risperidone ODT 4 mg (40 s). Reasons for slow dissolution of the olanzapine generics may include low product potency, excipient binding, excipient solubility, active ingredient particle size and incomplete disintegration.

Conclusions

Differences in the formulation and manufacturing process of olanzapine ODTs appear to have a strong influence on the disintegration time of the active compound; differences that may potentially impact their use in clinical practice.

Electronic supplementary material

The online version of this article (doi:10.1007/s40268-013-0030-8) contains supplementary material, which is available to authorized users.     

Medium-Term Effects of Insulin Degludec on Patients with Type?1 Diabetes Mellitus

Objective

The aim of this study was to analyze the changes in daily blood glucose fluctuation and insulin dose in patients with type 1 diabetes mellitus (T1DM) undergoing basal-bolus therapy following a switching of basal insulin used from insulin glargine or detemir to insulin degludec.

Methods

Seven patients with T1DM were enrolled. All patients treated with insulin glargine or detemir twice daily were switched to insulin degludec with 80–90 % of the prior insulin dose. During the study period, the basal insulin doses were adjusted by the attending physician. The patients underwent continuous glucose monitoring before, 3 days after, and 24 weeks after switching to insulin degludec. The daily insulin dose was analyzed before, 3 days after, and 24 weeks after switching. Glycated hemoglobin levels were measured before and 24 weeks after switching.

Results

The blood glucose profile did not change significantly before and after switching. On the other hand, the total daily insulin dose and total daily basal insulin dose decreased significantly 24 weeks after switching.

Discussion

In patients with T1DM undergoing insulin glargine or detemir treatment, it is possible to achieve similar glycemic control in the medium term with a once daily, lower dose of insulin degludec.     

An influence of adrenaline (1:80,000) containing local anesthesia (2% Xylocaine) on glycemic level of patients undergoing tooth extraction in Riyadh

Objective

Aim is to compare the glycemic level among patients before, and after local anesthesia containing adrenaline 1:80,000 among patients who need dental extraction.

Materials and methods

60 patients were randomly selected including 30 healthy and 30 with a diabetes history for this study in Riyadh city. First the blood glucose level was measured before administering local anesthesia containing adrenaline after taking their history with glucocheck according to instructions, then blood Sugar level was recorded after administering local anesthesia containing adrenaline 1:80,000 concentrations. Blood sugar level was also checked 5 min after the tooth extraction procedure.

Results

There were no significant results found after the administration of local anesthesia containing adrenaline in both healthy and diabetic patients (p > 0.05). However, change of significance (p < 0.05) was noticed in diabetic patients who had not taken their hypoglycemic medication; there was a rise in their blood glucose level after extraction.

Conclusion

The study concluded no significant effect on the glycemic level of patients after the administration of local anesthesia containing adrenaline 1:80,000 in healthy and diabetic patients whether hypoglycemic medication was taken or not but a rise in blood sugar level was found among diabetic patients who did not take their hypoglycemic medications undergoing tooth extraction.     

Evaluation of clinical activity and safety of Daflon 500 mg in type 2 diabetic female patients

Background

The incidence of cardiovascular disease in patients with type 2 diabetes mellitus is approximately twice as high as in the non-diabetic population.

Aim

To investigate the hypoglycemic and hypocholesterolemic effects of Daflon^® 500 mg (DF) administration together with its tolerability and efficacy in reducing the cardiovascular metabolic risk factors in female patients with type 2 diabetes.

Methods

In a well-adequate controlled single-blinded randomized parallel design the tolerability and the efficacy of Daflon^® (500 mg) either alone or with oral hypoglycemic, twice daily for 45 days, was studied in 36 female patients with type 2 diabetes.

Results

None of the patients in the studied groups were reported to have any adverse events throughout the treatment period (45 days), liver and kidney function tests were within normal limits and there was no significant difference between the pre-treatment (day 0) and post-treatment (day 45) values. Female patients receiving Daflon^® either alone or with oral hypoglycemic showed significant decrease in serum glucose; fructosamine; total cholesterol; LDL–cholesterol; triglycerides; malondialdehydes (as index of lipid peroxidation) and C-reactive protein (CRB) levels along with increase in the levels of nitric oxide and blood glutathione.

Conclusion

This study has shown that Daflon^® (500 mg, twice daily for 45 days) is helpful in reducing glucose level and the risk of cardiovascular disease in type 2 diabetic patients.

Recommendation

Further clinical trials are essential for strengthening the evidence base on the role of this drug in the cardiovascular risk in diabetic patients.     

Disposition and Metabolism of Setipiprant,a Selective Oral CRTH2 Antagonist,in Humans

Background

Setipiprant, a tetrahydropyridoindole derivative, is a CRTH2 (chemoattractant receptor-homologous molecule expressed on T-helper [Th]-2 cells) antagonist that has the potential to be effective in the treatment of patients with diseases with an allergic etiology, such as allergic rhinitis and asthma.

Objectives

This study investigated the disposition, metabolism, and elimination of setipiprant.

Study design

In this open-label study, a single oral dose of 1,000 mg ¹⁴C-labeled setipiprant was administered.

Participants

Six healthy male subjects were enrolled in this study.

Results

The radioactive dose was almost completely recovered in feces (88.2 %) and to a smaller extent in urine (11.7 %). The main recovery route for unchanged setipiprant was feces (50 % of the radioactive dose). The recovered amount of unchanged setipiprant in urine accounted for 3.7 %. The two main metabolites were M7 and M9 with the intact tetrahydropyridoindole core of setipiprant. M7 and M9 are supposedly two distinct dihydroxy-dihydronaphthalene isomers assumed to be formed by intermediate epoxidation of the naphthyl ring followed by a hydrolytic epoxide ring-opening. M7 and M9 accounted for 20.0 and 15.3 % of the administered radioactive dose. Both metabolites were mainly excreted via feces and to a lesser extent via urine. M7 was the only metabolite quantifiable in plasma, but at concentrations consistently below 10 % of those of the parent drug.

Conclusion

Setipiprant is mainly excreted in feces in the form of the parent drug and in smaller amounts as its metabolites M7 and M9.     

Massive Naproxen Overdose with Serial Serum Levels

Context

Massive naproxen overdose is not commonly reported. Severe metabolic acidosis and seizure have been described, but the use of renal replacement therapy has not been studied in the context of overdose.

Case Details

A 28-year-old man ingested 70 g of naproxen along with an unknown amount of alcohol in a suicidal attempt. On examination in the emergency department 90 min later, he was drowsy but had normal vital signs apart from sinus tachycardia. Serum naproxen level 90 min after ingestion was 1,580 mg/L (therapeutic range 25–75 mg/L). He developed metabolic acidosis requiring renal replacement therapy using sustained low efficiency dialysis (SLED) and continuous venovenous hemofiltration (CVVH) and had recurrent seizure activity requiring intubation within 4 h from ingestion. He recovered after 48 h.

Discussion

Massive naproxen overdose can present with serious toxicity including seizures, altered mental status, and metabolic acidosis.

Conclusion

Hemodialysis and renal replacement therapy may correct the acid base disturbance and provide support in cases of renal impairment in context of naproxen overdose, but further studies are needed to determine the extraction of naproxen.     

Single-Dose,Randomized, Open-Label,Two-Way,Crossover Bioequivalence Study of Two Formulations of Pregabalin 300?mg Hard Capsules in Healthy Volunteers Under Fasting Conditions

Aims

This bioequivalence study was conducted to assess the bioequivalence of two formulations, test and reference, of pregabalin 300 mg hard capsules, under fasting conditions.

Methods

This was a single-center, randomized, single-dose, open-label, laboratory-blinded, two-way crossover study, with a minimum washout period of 7 days. Plasma samples were collected prior to and up to 36 h after dosing. Pregabalin plasma concentrations were determined, using a validated method, by reversed phase high performance liquid chromatography coupled to a tandem mass spectrometry detector (LC–MS–MS). Pharmacokinetic metrics used for bioequivalence assessment were the AUC_(0–t) (area under the plasma concentration–time curve from time zero to time of last observed non-zero plasma concentration) and the C_max (maximum observed plasma concentration). These parameters were determined from the pregabalin plasma concentration data using noncompartmental analysis.

Results

Forty healthy subjects, age ranging from 18 to 43 years old, were enrolled and randomized, of whom 39 completed the study. The ratio of geometric least square means for C_max was 99.29 % (90 % confidence interval [CI] 93.29–105.67). The ratio of geometric least square means for AUC_(0–t) was 101.54 % (90 % CI 100.13–102.98). The 90 % CIs were within the predefined range (80.00–125.00).

Conclusions

Bioequivalence between test and reference formulations, under fasting conditions, was concluded both in terms of rate and extent of absorption.     

Saudi young patient understanding of information about side effects: Verbal versus numerical expression

Objective

To determine the effect of providing different formats about side effect information (verbal versus numerical) to acne patients in Saudi Arabia that are newly prescribed Roaccutane.

Design

A prospective study assessing patients’ degree of estimation about side effect information.

Participants

One hundred and forty-one acne patients newly prescribed Roaccutane.

Settings

Four dermatology clinics in Riyadh. Two in tertiary hospitals and the other two in private clinics.

Intervention

Each patient received information about two different side effects for Roaccutane. The side effect provided was supplemented with the probability of occurrence, which was written either in words or in numbers. (Dry eye “very common” or “30%”; Loss of hair “rare” or “0.01%”).

Main outcome measures

Patient’s estimation of side effect occurrence. Other outcomes were the likelihood of experiencing the side effect, the severity of the side effect, their perception of risk of the side effects to their general health, their satisfaction with the information provided and, whether the information provided will influence their decision to take the medicine.

Result

The mean estimate for side effect occurrence for the dry eyes was 46% in the verbal group and 41% in the numerical group (p = 0.5); for loss of hair it was 50% in the verbal group and 39% in the numerical group (p = 0.03). There are no significant differences between verbal and numerical groups regarding the remaining measures.

Conclusion

Patients overestimate the probability of occurrence of side effect. Verbal format of probability of occurrence is associated with higher estimation than the numerical format.     

Efficacy and Safety of a Lercanidipine/Enalapril Fixed-Dose Combination in Hypertensive Patients in Portugal

Background

Fixed-dose combinations of hypertensive drugs have been advocated as a suitable option for hypertensive patients who require two or more drugs to achieve blood pressure (BP) targets.

Objectives

Our objective was to assess the efficacy and safety of lercanidipine/enalapril in clinical practice.

Methods

This observational study collected data for patients with hypertension treated by 46 specialists at clinics across Portugal with lercanidipine/enalapril (10/20 mg). The primary outcome measure was the reduction from baseline in systolic BP (SBP) and diastolic BP (DBP).

Results

The registry enrolled 315 patients (59.1 % females; mean age 64.84 ± 12.18 years). Baseline SBP and DBP were 159.11 ± 16.93 and 88.32 ± 12.35 mmHg, respectively. At a mean 2.88 ± 1.75 months after starting lercanidipine/enalapril, the mean change from baseline in SBP and DBP were −18.08 ± 15.91 and −10.10 ± 11.46 mmHg, respectively (both p < 0.001). This corresponded to reductions of 11.4 and 11.3 % in SBP and DBP, respectively. SBP was reduced independently of sex and age, and DBP was reduced independently of sex. The BP control (<140/90 mmHg) rate significantly increased from 10.2 % at baseline to 51.0 % after a mean of 2.88 months of treatment with lercanidipine/enalapril (p < 0.001). Adverse effects were seen in only one patient (0.3 %), who developed a persistent dry cough.

Conclusions

Treatment with the fixed-dose combination lercanidipine/enalapril was associated with significant reductions in SBP and DBP, and a significant increase in the BP control rate. This fixed-dose combination has been shown to effectively reduce BP, generally independently of age and sex, and with an excellent safety profile.