Inaccurate Dosing Research Articles

A simple endoscopic method with radial endobronchial ultrasonography for low-migration rate coil-tailed fiducial marker placement.

BackgroundFiducial markers (FMs) are useful for tracking small peripheral lung nodules (PLN) before stereotactic radiotherapy, but migration over the course of treatment may result in inaccurate dosing to the tumor. To minimize FM migration, coil-tailed FMs have been designed. Our objective was to assess both the feasibility of radial endobronchial ultrasonography (r-EBUS) placement and the migration rate of coil-tailed FMs.MethodsIn this retrospective study, we included patients who received r-EBUS guided placement of coil-tailed FMs for PLN <25 mm from June 2015 to May 2018. We introduced the FM into the nodule with the use of bronchial brush, without fluoroscopy.ResultsThirty patients had r-EBUS guided placement of a coil-tailed FM before stereotactic radiation therapy. Nodule’s median long- and short-axis diameters were 15 mm (8–25 mm) and 8 mm (5–20 mm), respectively; short diameter of 27 nodules (90%) was less than 15 mm. All nodules were reached and visualized with r-EBUS, with an ultrasound (US) signal showing a centered or tangential probe in 26 and 4 cases, respectively. No immediate complication was reported. Twenty-three patients had stereotactic radiation therapy within a median time of 29 days (14–126 days). No FM migration occurred between r-EBUS placement and radiotherapy. Pre-treatment planning and 3-month follow-up CT scans showed that all FMs stayed in direct contact with the lesions.Conclusionsr-EBUS is a safe procedure for the placement of nitinol coil FMs, which have a low migration rate.

Evaluation of human immunodeficiency virus medication errors in a community hospital following the implementation of a pharmacist‐led antiretroviral stewardship program

AbstractIntroductionCombination antiretroviral therapy has greatly improved survivability in people living with human immunodeficiency virus (PLWH); however, medication‐related problems can attenuate virologic suppression and lead to therapeutic failure and drug resistance. The prevalence of antiretroviral (ARV) medication errors in hospitalized PLWH is highly variable, but it is clear that the potential for errors increases with the transition to inpatient care. Pharmacist‐led ARV stewardship programs in large, academic institutions have demonstrated reductions in ARV errors during hospitalizations, but the feasibility of such programs in smaller, community hospitals in the Deep South remains unclear.MethodsWe conducted a retrospective quasi‐experimental study of non‐pregnant, adult PLWH admitted to a community hospital between 2014 and 2018. The primary objective was to compare the percentage of admissions associated with a composite of ARV medication errors (inappropriate regimens, inaccurate dosing, delayed dosing, and major drug‐drug interactions [DDIs]) before and after implementation of an ARV stewardship program.ResultsThe percentage of admissions associated with the primary composite of ARV medication errors decreased by 70% between the pre‐intervention (56 [70%] of 80 admissions) and post‐intervention period (13 [21.3%] of 61 admissions). The percentage of admissions associated with inappropriate ART regimens, major DDIs, and multiple ARV errors all decreased by more than 80%. There was no significant difference in the percentage of admissions associated with renal, non‐renal, or delayed dosing errors despite an overall decrease in error frequency.DiscussionA significant reduction in ARV medication error rates comparable to those reported in similar studies conducted at large, academic institutions was observed. The impact of this innovative pharmacist‐led ARV stewardship program provides additional evidence of the effectiveness of such programs in community hospitals with modest personnel resources.

Do owners administer inappropriate doses of anthelmintic based on an inaccurate perception of their horse's bodyweight?

Background: Inaccurate dosing and repeated administration of anthelmintic from the same drug class are indicated as factors associated with equine helminth resistance; and resistance is specifically related to the under-dosing of anthelmintic products. Research indicates that many owners may still rely on visual estimation to determine a horse's bodyweight. Aim: The pilot study aimed to investigate whether owners administer inappropriate doses of anthelmintic based on an inaccurate perception of their horse's bodyweight. Method: Data were collected from 16 horse owners with varying experience and from a variety of equine disciplines. A series of questions were presented in order to capture specific information. Owners were asked to provide the dose of anthelmintic (kg) that they had most recently administered to their horse, to estimate the bodyweight of their horse, and to provide a body condition score (BCS) for their horse using the guide provided. Each horse was then weighed on an equine weighbridge to obtain an accurate bodyweight. The estimated bodyweight was compared with that of the accurate bodyweight, and the most recently administered dose of anthelmintic was compared with both the estimated bodyweight and the accurate bodyweight. The BCS provided by each owner was compared with that of the BCS provided by the researcher. Data were tested for normal distribution using a Shapiro-Wilks test, and analysed using an independent-samples t-test or a paired-samples t-test. Results: All of the owners inaccurately estimated the bodyweight of their horse, however there was no statistically significant difference between the estimated bodyweight and the accurate bodyweight (p=0.738). Owners with less experience more accurately estimated the bodyweight of their horse when compared with owners with more experience, but there was no statistically significant difference in accuracy between the two groups (p=0.085). There was no statistically significant difference between the accurate bodyweight and the dose of anthelmintic that owners had administered to their horse (p=0.074), but there was a statistically significant difference between the estimated bodyweight and the dose of anthelmintic that owners had administered to their horse (p=0.034). Conclusion: Horse owners administer inappropriate doses of equine anthelmintic based on an inaccurate perception of their horse's bodyweight, however the horse's estimated bodyweight does not appear to be the only influencing factor when deciding on the dose of anthelmintic to be administered.

Modeling Ketogenesis for Use in Pediatric Diabetes Simulation.

Simulation is being increasingly integrated into medical education. Diabetes simulation is well-received by trainees and has demonstrated improved clinical results, including reduced adult inpatient hyperglycemia. However, no pediatric-specific diabetes simulation programs exist for use in medical education. None of the existing diabetes models incorporate ketones as an input or an output, which is essential for use in teaching pediatric diabetes management. We created a pediatric diabetes simulation incorporating both blood sugar and urine ketones as output. Ketone output is implemented as a state variable but is obfuscated to simulate hospital experience. Blood sugar output is similar to other models and incorporates the current blood sugar, insulin on board (IOB) and carbohydrates on board (COB), and insulin and carbohydrate sensitivities. The program calculates all IOB and COB every 15 minutes based on user input and provides written summary feedback at the end of the simulation about inaccurate dosing and timing. The simulation realistically incorporated both blood glucose and urine ketones in clinically valid and actionable formats. After completing this simulation, 16/17 pediatric residents indicated that they wanted more simulated diabetes cases integrated into their curriculum. Implementing simulation into pediatric diabetes education was feasible and well-received. More work is needed to further study the role of simulation in pediatric diabetes education when used adjunctively or in lieu of lectures when time or resources are limited.

Can we predict trends in tribo-charging of pharmaceutical materials from first principles?

Tribo-charging can negatively impact safety and efficacy of pharmaceutical products due to particle agglomeration and adherence to surfaces resulting in poor mixing and inaccurate dosing. Prediction of relative charging trends in-silico and from first principles could provide an efficient tool for guiding development during early formulation studies. We experimentally investigate tribo-charging of pharmaceutical compounds and compare the results with energies from electronic-structure-calculations. Calculations were performed applying different levels of theory (semi-empirical and DFT with different functionals) to estimate properties including ionization potentials (IP), and work functions (WF). The calculations are performed for single molecules assuming that, at least, relative properties of the solid phase are reproduced. Our results suggest that, independently of the level of theory, calculated IP values correlate well with experimental tribo-charging trends provided we use the adiabatic IP. By comparison, WF values, calculated by a commonly used approximation, turn out being a poor descriptor for tribo-charging trends.

Vancomycin dosing in hospitalized children by weight status: a systematic review

Purpose In children, providers commonly use total body weight for calculating the appropriate medication dose. However, variability in body composition may cause inaccurate dosing. Children with obesity have greater fat mass, higher total body water percentage, and greater fat-free mass than children at a normal weight. Vancomycin is a commonly prescribed medication in hospitalized pediatric patients that carries potential for significant harm with both overdosing or underdosing. This study aimed to determine whether children having overweight or obesity have increased vancomycin levels compared with children …

Pharmacokinetics of Second-Line Anti-Tubercular Drugs.

Multidrug-resistant tuberculosis (MDR TB) has become a major global health concern and is also an issue in children. Children with MDR TB need longer duration of treatment with multiple drugs. The MDR TB treatment regimen usually comprises of a fluoroquinolone, an aminoglycoside, ethionamide, cycloserine, pyrazinamide and ethambutol. In the absence of pediatric friendly tablets/formulations, in most cases the adult tablets are either crushed or broken. This is likely to lead to inaccurate dosing. Very limited information is available on the pharmacokinetics of second-line anti-TB drugs in children with MDR TB, except for few studies from South Africa and one from India. Drugs such as linezolid, clofazimine are also being considered for the treatment of MDR TB in children. However, their pharmacokinetics is not known in the pediatric population. It is important to generate pharmacokinetic studies of drugs used to treat MDR TB in children in different settings, which would provide useful information on the adequacy of drug doses.

Interventions to assist parents and caregivers in accurately dosing liquid medications for their children: a scoping review

Background Parents’ inaccurate dosing of liquid medications for their children is common, resulting in treatment failure and adverse effects.

Female low dose tip syringes-increased complexity of use may compromise dosing accuracy in paediatric patients.

The International Organization for Standardization (ISO) created enteral device specifications to reduce tubing misconnections. The Global Enteral Device Supplier Association (GEDSA) supports a female design: standard and low dose tip (LDT). Concerns include increased complexity of use with adapters, dosing accuracy and workflow. No peer-reviewed studies have evaluated dosing accuracy of the complete female system with adapters. The objective of this study was to compare dosing accuracy of the female design to legacy syringes. An in vitro study was conducted at the University of Florida College of Pharmacy pharmaceutics laboratory. Assessments were completed for syringe size, dispense methods and volumes, and adapters when applicable. A gravimetric scale and specific gravity were used to calculate administration volumes. The primary outcome was frequency administration volume exceeded 10% expected amount. A total of 576 tests were performed. The LDT resulted in significantly higher rates of unacceptable dosing variance compared to legacy (21.2% vs 7.4%, P=0.003). Variance exceeding 10% occurred more frequently with LDT 0.5 and 1mL syringes, medication cup dispensing (liquid or tablet) and inappropriate LDT adapter use. Unapproved adapter processes compared to FDA-approved processes held a higher likelihood of unacceptable dosing variance (28% vs 7.4%, P<0.001). FDA-approved use of adapters with prefilled syringes compared to bedside administration may result in higher rates of dosing inaccuracy (18.8% vs 5.6%, P=0.06). This study raises clinical concerns of dosing inaccuracies with the LDT syringes, particularly with 0.5 and 1mL sizes. The use of adapters significantly increases the opportunity for inaccurate dosing.

A research pathway for the study of the delivery and disposition of nebulised antibiotics: an incremental approach from in vitro to large animal models

BackgroundNebulised antibiotics are frequently used for the prevention or treatment of ventilator-associated pneumonia. Many factors may influence pulmonary drug concentrations with inaccurate dosing schedules potentially leading to therapeutic failure and/or the emergence of antibiotic resistance. We describe a research pathway for studying the pharmacokinetics of a nebulised antibiotic during mechanical ventilation using in vitro methods and ovine models, using tobramycin as the study antibiotic.MethodsIn vitro studies using a laser diffractometer and a bacterial-viral filter were used to measure the effect of the type and size of tracheal tubes and antibiotic concentration on the particle size distribution of the tobramycin 400 mg (4 ml; 100 mg/ml) and 160 mg (4 ml, 40 mg/ml) aerosol and nebulised mass delivered. To compare the regional drug distribution in the lung of two routes (intravenous and nebulised) of drug administration of tobramycin 400 mg, technetium-99m-labelled tobramycin 400 mg with planar nuclear medicine imaging was used in a mechanically ventilated ovine model. To measure tobramycin concentrations by intravenous and nebulised tobramycin 400 mg (4 ml, 100 mg/ml) administration in the lung interstitial space (ISF) fluid and blood of mechanically ventilated sheep, the microdialysis technique was used over an 8-h duration.ResultsTobramycin 100 mg/ml achieved a higher lung dose (121.3 mg) compared to 40 mg/ml (41.3 mg) solution. The imaging study with labelled tobramycin indicated that nebulised tobramycin distributed more extensively into each lung zone of the mechanically ventilated sheep than intravenous administration. A higher lung ISF peak concentration of tobramycin was observed with nebulised tobramycin (40.8 mg/l) compared to intravenous route (19.0 mg/l).ConclusionsThe research methods appear promising to describe lung pharmacokinetics for formulations intended for nebulisation during mechanical ventilation. These methods need further validation in an experimental pneumonia model to be able to contribute toward optimising dosing regimens to inform clinical trials and/or clinical use.

INTERVENTIONS TO ASSIST PARENTS IN ACCURATELY DOSING LIQUID MEDICATIONS FOR THEIR CHILDREN: A SCOPING REVIEW

Abstract BACKGROUND Parents’ inaccurate dosing of liquid medications for their children is common, resulting in treatment failure and potential adverse effects. Educational interventions delivered by health care professionals are a means to help parents properly administer liquid medications. OBJECTIVES This scoping review was conducted to identify and describe empirically researched educational interventions that prevent inaccurate dosing of liquid medications by parents of children less than 12 years old. DESIGN/METHODS We conducted a scoping review using the Joanna Briggs Institute Methodology for Scoping Reviews. With assistance from a library scientist, we searched PubMed, CINAHL, and Web of Science for English-language articles published before June 2017. We also looked at the reference lists of the included articles and subsequent articles that have cited them to identify additional studies (forward and backward searching). Two reviewers independently screened the retrieved titles and abstracts using predetermined criteria. Only quantitative, empirically designed studies that examined interventions delivered by health care professionals to help parents of children under 12 years old to accurately dose liquid medications were included. We appraised the quality of the included articles using the mixed methods appraisal tool (MMAT) and conducted a thematic analysis to identify trends and patterns. RESULTS Of the 180 abstracts identified in the search strategy, 9 studies met our inclusion criteria. We identified four main types of interventions: 1. use of visual aids (n=6); 2. use of advanced counselling strategies (n=2); 3. use of standardized measuring tools (n=3); and, 4. use of standardized units of measurement (n=2). Some studies evaluated more than one type of intervention. The overall quality of the included studies was moderate, with 11.1% (n=1) scoring 0.25, 33.3% (n=3) scoring 0.50, 55.6% (n=5) scoring 0.75, and none scoring 1.0. CONCLUSION Dosing accuracy of liquid medication for children by their parents is an important topic. More high quality studies conducted by a variety of research groups are needed to ensure the development and implementation of effective evidence-based educational interventions. There is a lack of standardization in the definition of a dosing error. Consensus regarding a standard definition would help studies be more comparable.

International survey on high- and low-dose synacthen test and assessment of accuracy in preparing low-dose synacthen.

The short synacthen test (SST) is widely used to assess patients for adrenal insufficiency, but the frequency and protocols used across different centres for the low-dose test (LDT) are unknown. This study aimed to survey centres and test the accuracy of ten different synacthen preparation strategies used for the LDT. Members of 6 international endocrine societies were surveyed regarding diagnostic tests used for adrenal insufficiency, and in particular the SST. Synacthen was diluted for the LDT and concentrations measured using a synacthen ELISA. Survey responses were received from 766 individuals across 60 countries (52% adult, 45% paediatric endocrinologists). The SST is used by 98% of centres: 92% using high-dose (250μg), 43% low-dose and 37% both. Ten low-dose dilution methods were assessed and variation in synacthen concentration was demonstrated with intramethod coefficients of variation (CV) ranging from 2.1% to 109%. The method using 5% dextrose as a diluent was the least variable (CV of 2.1%). The variation in dilution methods means that the dose of synacthen administered in a LDT may vary between 0.16 and 0.81μg. The high-dose SST is the most popular diagnostic test of adrenal insufficiency, but up to 72% of paediatric endocrinologists use a LDT. There is considerable variation observed both within and between low-dose synacthen dilution methods creating considerable risk of inaccurate dosing and thereby invalid results.

Recording patient bodyweight in hospitals: are we doing well enough?

Recording patient weight is a standard practice for all hospital admissions, with this measurement influencing other daily practices that rely on the delivery of safe and effective patient care. Patient weight is important in the areas of medication prescribing, fluid balance and assessment of nutrition. In particular, prescribing narrow therapeutic index medications may result in significant harm as a potential consequence of inaccurate dosing. Despite its importance, it is evident that bodyweight measurements are recorded in only 13.5-55% of hospital patients, in a variety of settings including the emergency department, intensive care unit, medical and surgical wards. Barriers to compliance of healthcare staff include additional workload, patient handling and availability of appropriate weighing equipment. Hospitals and patients would benefit from enhancing compliance with the systematic weighing of patients, staff training and removing barriers to performing this task.

Assessment of inappropriate antibiotic use in pediatric patients: Point-prevalence study

This study aimed to determine inappropriate antibiotic use in a children's hospital using the point-surveillance method. One hundred thirteen hospitalized patients were included in the study on the study day. In all patients, data regarding age, sex, antibiotic use, type and dose of antibiotic if used, multiple antibiotic use, presence or absence of consultation with infectious diseases specialist before initiation of antibiotic, form of antibiotic use (empiric, targeted or prophylactic), and reason for antibiotic use were recorded. Inappropriate antibiotic use was determined by an infectious diseases specialist. The rate of antibiotic use was 70.8%. Of the patients receiving antibiotics, 43% were using more than one antibiotic. It was found that 73.7% of antibiotics were prescribed for empiric purposes and 14.3% for targeted therapy, whereas 12% were prescribed for prophylactic purposes. The rate of inappropriate antibiotic use was 33.8% among patients who were given antibiotics. Unnecessary antibiotic prescription was the most common cause for inappropriate antibiotic use (51.9%), followed by unnecessary multiple antibiotic use (29.6%), inaccurate dosing (11.1%), use of broader spectrum than required (7.4%), and use of antibiotics with narrower spectrum than needed (3.7%). The rate of inappropriate antibiotic use was significantly lower in antibiotics that required confirmation by an infectious diseases specialist (6.7%) than those not requiring confirmation (26.3%; p=0.023). The rate of inappropriate antibiotic use was significantly lower in antibiotics prescribed by infectious diseases specialists (8.6%) than those prescribed by other physicians (26.5%, p=0.027). Antibiotic use based on consultation with an infectious diseases specialist decreased inappropriate antibiotic use.

Syringe-feeding as a novel delivery method for accurate individual dosing of probiotics in rats.

Probiotic administration to rodents is typically achieved using oral gavage or water bottles, but both approaches may compromise animal welfare, bacterial viability, dosing accuracy, or ease of administration. Oral gavage dosing may induce stress, especially when given daily over several weeks, and cannot be performed by inexperienced personnel. Delivery in water bottles does not take multiple co-housed animals into account, leading to inaccurate dosing of individual rats. Moreover, slow consumption of the solutions over several hours may lead to variability in bacterial stability, and potential leftovers or clogging of the bottle further threaten the reliability of this method. To date, no method has been described that can provide non-stressful precise dosing of probiotics or prebiotics in individual rats. In accordance with the 3R principles (replace, reduce, refine), we propose syringe-feeding as a refinement method for simple yet accurate administration of probiotics. Animals hereby voluntarily consume the solution directly from a syringe held into their home cage, thereby enabling controlled dosing of individual animals. This method requires a short training phase of approximately 3 days, but is very fast thereafter, only taking seconds per rat. Since studies using probiotics are usually long-term experiments, we consider syringe-feeding the most appropriate probiotic delivery mode available to date.

Validity of Broselow tape for estimating weight of Indian children.

Background & objectives:The Broselow tape has been validated in both ambulatory and simulated emergency situations in the United States and is believed to reduce complications arising from inaccurate drug dosing and equipment sizing in paediatric population. This study was conducted to determine the relationship between the actual weight and weight determined by Broselow tape in the Indian children and to derive an equation for determination of weight based on height in the Indian children.Methods:This cross-sectional study was conducted at a tertiary care hospital in Mumbai, India. The participants’ weights were divided into three groups <10 kg, 10-18 kg and >18 kg with a total sample size estimated to be 210 (70 in each group). Using the tape, the measured weight was compared to Broselow-predicted weight and percentage weight was calculated. Accuracy was defined as agreement on Broselow colour-coded zones, as well as agreement within 10 per cent between the measured and Broselow-predicted weights. The resulting data were compared with weights estimated by advanced paediatric life support (APLS) and updated APLS formulae using Pearson's correlation coefficient.Results:The mean percentage differences were −11.78, −17.09 and −14.27 per cent for <10, 10-18 and >18 kg weight-based groups, respectively. The Broselow colour-coded zone agreement was 33.3 per cent in children weighing <10 kg, but only 7.4 per cent in the 10-18 kg group and 33.9 per cent in the >18 kg group. Agreement within 10 per cent was 53.13 per cent for the <10 kg group, but only 21.08 per cent for the 10-18 kg group and 33.9 per cent for the >18 kg group. Application of 10 per cent weight correction factor improved the percentages to 79.2 per cent for the <10 kg category, to 55.70 per cent for the 10-18 kg group and to 61.0 per cent for the >18 kg group. The correlation coefficient between actual weight and weights estimated by Broselow tape (r=0.89) was higher than that between actual weight and weight estimated by APLS method or updated APLS formulae (r=0.68) in 12-60 months age group as well as in >60 months age group (r=0.76).Interpretation & conclusions:Broselow weight overestimated weight by >10 per cent in majority of Indian children. The weight overestimation was greater in children belonging to over 18 and 10-18 kg weight groups. Applying 10 per cent weight correction factor to the Broselow-predicted weight may provide a more accurate estimation of actual weight in children attending public hospital. Weights estimated using Broselow tape correlated better with actual weights than those calculated using APLS and updated APLS formulae.

Adherence to acute otitis media diagnosis and treatment guidelines among Israeli otolaryngologists

IntroductionThe recent Israeli acute otitis media (AOM) guidelines, drafted mainly by pediatricians and family physicians in 2013, addressed diagnostic and therapeutic issues, in order to reduce over-diagnosis and treatment. These guidelines are considered as the 'standard of care' for AOM management. While the adherence rate of pediatricians to previous Israeli AOM guidelines (2004) was reported to be high (>85%), the compliance of otolaryngologists has not been studied. MethodsAn anonymous 19-item questionnaire was circulated among practicing Israeli otolaryngologists (residents [n = 93], specialists [n = 283]). All the items were scored according to the number of correct answers in line with the guidelines, and summed on a 0–100 scale. ResultsResponse rate was 34% (n = 127). Overall, scores of correct answers of residents (n = 48, 52% of all residents) and specialists (n = 79, 28% of all specialists) were similar, and showed comparable moderate adherence to both guidelines: 55.7 vs 58.3 (p = 0.26). Residents were more likely to adhere to the U.S. guidelines, when compared to specialists (score difference 6.1 vs 2.8, p = 0.008). Responders preferred the microscope for diagnosis (48%), over the recommended (pneumatic) otoscope (62%) (p = 0.05), and were more likely to start antibiotic therapy (62%), rather than the 'watchful waiting’ (38%) (p = 0.03). Concerning antibiotic treatment, 50% of otolaryngologists prescribed amoxicillin as recommended, at 60–80 mg/kg/d. ConclusionThe moderate adherence rate suggests that the guidelines were partially adopted by otolaryngologists, who use different instrumentation than recommended, and treat more severe/complicated cases. Over-treatment with antibiotics and inaccurate dosing regimens are still common. Better implementation of the AOM guidelines among otolaryngologists should be performed in designated training platforms.

Accuracy of intravenous and enteral preparations involving small volumes for paediatric use: a review

BackgroundChildren often need to be administered very small volumes of medicines that are authorised for use in adults. Neonatal drug delivery is particularly challenging, and doses are often immeasurable with...

A Population Pharmacokinetic Model for 51Cr EDTA to Estimate Renal Function

51Cr EDTA clearance (CL) from plasma is used to estimate glomerular filtration rate (GFR). We propose that current methods for analysing the raw 51Cr EDTA measurements over-simplifies the disposition of 51Cr EDTA and therefore could produce biased GFR estimates. The aim of this study was to develop a population pharmacokinetic model for 51Cr EDTA disposition and to compare model-predicted GFR to other methods of estimating renal function. Data from 40 individuals who received ~7.4MBq of 51Cr EDTA, as an intravenous bolus, were available for analysis. Plasma radioactivity (counts/min) was measured from timed collection points at 2, 4, 6 and 24h after the dose. A population analysis was conducted using NONMEM® version 7.2. Model-predicted GFR was compared with other methods for estimating renal function using mean prediction error (MPE). A two-compartment pharmacokinetic model with first-order elimination best fit the data. Compared with the model predictions, creatinine CL from 24h urine data was unbiased. The commonly used 'slope-intercept' method for estimating isotopic GFR was positively biased compared with the model (MPE 15.5mL/min/1.73m2 [95% confidence interval {CI} 8.9-22.2]. The Cockcroft Gault, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equations led to negatively biased GFR estimates (MPE -19.0 [95% CI -25.4 to -12.7], -20.1 [95% CI -27.2 to -13.1] and -16.5 [95% CI -22.2 to -10.1] mL/min/1.73m2, respectively). The biased GFR estimates were most obvious in patients with relatively normal renal function. This may lead to inaccurate dosing in patients who are receiving drugs with a narrow therapeutic range where dosing is adjusted according to GFR estimates (e.g. carboplatin). The study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), number: ACTRN 12611000035921.

Riluzole 5 mg/mL oral suspension: for optimized drug delivery in amyotrophic lateral sclerosis.

The aim of the present work is to extensively evaluate the pharmaceutical attributes of currently available riluzole presentations. The article describes the limitations and risks associated with the administration of crushed tablets, including the potential for inaccurate dosing and reduced rate of absorption when riluzole is administered with high-fat foods, and the advantages that a recently approved innovative oral liquid form of riluzole confers on amyotrophic lateral sclerosis (ALS) patients. The article further evaluates the patented and innovative controlled flocculation technology used in the pseudoplastic suspension formulation to reduce the oral anesthesia seen with crushed tablets, resulting in optimized drug delivery for riluzole. Riluzole is the only drug licensed for treating ALS, which is the most common form of motor neurone disease and a highly devastating neurodegenerative condition. The licensed indication is to extend life or the time to mechanical ventilation. Until recently, riluzole was only available as an oral tablet dosage form in the UK; however, an innovative oral liquid form, Teglutik® 5 mg/mL oral suspension, is now available. An oral liquid formulation provides an important therapeutic option for patients with ALS, >80% of who may become unable to swallow solid oral dosage forms due to disease-related dysphagia. Prior to the launch of riluzole oral suspension, the only way for many patients to continue to take riluzole as their disease progressed was through crushed tablets. A novel suspension formulation enables more accurate dosing and consistent ongoing administration of riluzole. There are clear and important advantages such as enhanced patient compliance compared with crushed tablets administered with food or via an enteral feeding tube and the potential for an improved therapeutic outcome and enhanced quality of life for ALS patients.