Extended stability of ascorbic acid in 5% dextrose injection and 0.9% sodium chloride injection.
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Ascorbic Acid↗
Biomedical subjects
Mark A Gill
Publications and source records attributed to Mark A Gill.
Stability of advanced life support drugs in the field.
PURPOSE: The effects of wide temperature variations on the stability of atropine, epinephrine, and lidocaine stored under field conditions in advanced life support (ALS) paramedic units were evaluated. METHODS: Vehicles from various ALS paramedic units were selected throughout Los Angeles County, California, including desert, marine, and helicopter-based divisions. A temperature-recording device was placed in the compartment where drugs are stored and used to record and store temperature data at 15-minute intervals. Three autoinjector-style syringes of atropine, epinephrine, and lidocaine were taken from stock for each ALS unit and placed in each vehicle, while three control syringes were stored in the laboratory under controlled conditions. Six samples of each drug were withdrawn at time 0 and on days 5, 10, 15, 30, and 45. Samples were analyzed using high-performance liquid chromatography. Stock solutions, created using analytical grade atropine, epinephrine, and lidocaine, were used to construct 5-point standard curves to determine the drug concentration of each sample. RESULTS: Seven sites exceeded 104 degrees F (40 degrees C) for as little as 30 minutes and as long as 795 minutes. Ten of the sites achieved a mean kinetic temperature (MKT) above 77 degrees F (25 degrees C), with the highest MKT calculated being 84.1 degrees F (28.9 degrees C) over a 45-day period. There was no evidence of drug degradation at any site, at any temperature, or at any time point. CONCLUSION: Atropine, epinephrine, and lidocaine can be stored at temperatures of up to 84.1 degrees F (28.9 degrees C) for up to 45 days and tolerate temperature spikes of up to 125 degrees F (51.7 degrees C) for a cumulative time of 795 minutes (13.25 hours) without undergoing degradation.
Advanced Cardiac Life Support↗
Imipenem levels are not predictable in the critically ill patient.
BACKGROUND: Critically ill patients often demonstrate extremely unusual volumes of distribution (Vd) and half-lives (t1/2) of drugs. Imipenem is a widely used antibiotic in critically ill patients. METHODS: We performed high-performance liquid chromatography analysis of imipenem in samples from 50 critically ill patients treated with either 500 or 1,000 mg. RESULTS: Peak imipenem levels varied from 1.56 microg/mL to 58.8 microg/mL. Trough levels varied between 0.0 microg/mL and 15.62 microg/mL. Only 54% of patients maintained a trough level greater than 4 microg/mL. Both the Vd and the t1/2 of imipenem were much greater than observed in other patient populations. CONCLUSION: The pharmacokinetic activity of imipenem in critically ill patients is different from that in other patient populations. There is a very weak correlation between dosage and serum concentrations. Therapeutic failures of imipenem may be because of unpredictable pharmacodynamics (Vd and t1/2) in critically ill surgical patients.
APACHE↗
Pharmacokinetics of Ibuprofen in children with cystic fibrosis.
An exaggerated inflammatory response is responsible for the decline of lung function in patients with cystic fibrosis (CF). Ibuprofen is a potent anti-inflammatory agent that demonstrates inhibition of neutrophil activity in vitro at concentrations between 50 and 100 mg/L, whereas lower concentrations result in an increase in inflammatory mediators. Significant decline in the rate of deterioration of pulmonary function and increased nutritional status were observed in children with CF who were administered long-term high-dosage ibuprofen therapy. As with many other drugs, CF patients appear to exhibit altered pharmacokinetics of ibuprofen (reduced bioavailability, increased volume of distribution, and more rapid clearance) when compared with healthy controls. However, the absence of studies with intravenous ibuprofen as well as protein binding measurements in patients with CF currently limits the ability to compare the pharmacokinetics with those in other populations. Current studies indicate that there is high interpatient variability in ibuprofen pharmacokinetics among CF patients. Some of this variability can be explained by differences in ibuprofen formulation administered. Therapeutic drug monitoring of high-dosage ibuprofen therapy is recommended because of the biphasic response to inflammatory mediators demonstrated in vitro as well as the high interpatient variability in pharmacokinetics. Due to the differences in absorption characteristics between ibuprofen formulations, the timing of obtaining blood samples for pharmacokinetic analysis is critical. Maximum a posteriori Bayesian analysis has been shown to provide more accurate and precise estimates of the pharmacokinetic parameters of ibuprofen in children with CF, and may also be a useful tool to further investigate the relationship between measures of drug exposure and efficacy/toxicity outcomes.
Anti-Inflammatory Agents, Non-Steroidal↗
Visual compatibility of risperidone solution and lithium citrate syrup.
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Administration, Oral↗
A review of rivastigmine: a reversible cholinesterase inhibitor.
BACKGROUND: Rivastigmine tartrate is a reversible cholinesterase inhibitor indicated for the symptomatic treatment of mild to moderate dementia. It was approved by the US Food and Drug Administration for the treatment of Alzheimer's disease (AD) on April 21, 2000. OBJECTIVE: The purpose of this review was to summarize the background on dementia of the Alzheimer type and the pharmacokinetic properties, efficacy and tolerability profiles, clinical applications, adverse effects (AEs), drug interactions, and pharmacoeconomics of rivastigmine. METHODS: A literature search was conducted using MEDLINE (1995-2002), EMBASE Geriatrics and Gerontology (1995-2002), the National Institutes of Health Alzheimer's Disease Education and Resource Center Combined Health Information Database, and Google. Search terms included rivastigmine, Exelon, ENA 713, and ENA-713. The bibliographies of retrieved articles also were searched for relevant articles. RESULTS: In clinical trials, rivastigmine has improved or maintained cognitive function, global function (ie, activities of daily living [ADLs]), and behavior in patients with mild to moderate AD for up to 52 weeks. AEs are generally mild to moderate and primarily affect the gastrointestinal (GI) tract. Clinically significant drug interactions with rivastigmine have thus far not been reported. Treatment with rivastigmine for up to 2 years may reduce the cost of caring for patients with AD. Cost savings are minimal during the first year, particularly for those with mild disease, but increase during the second year of treatment. Cost savings occur earlier for those with moderate AD. Most savings are realized from a delay in the need for institutionalization. CONCLUSIONS: Rivastigmine has been shown to improve or maintain patients' performance in 3 major domains: cognitive function, global function (ADLs), and behavior. The efficacy and tolerability of rivastigmine have been proved by numerous clinical trials, with the most prominent AE being GI irritation.
Alzheimer Disease↗
Stability and antibacterial activity of cefepime during continuous infusion.
The stability of cefepime during simulated continuous infusion was determined with a motorized portable infusion pump worn over a period of 24 to 36 h. Susceptibility testing on cefepime solutions over time indicates that the degradation products do not exhibit antibacterial activity. Cefepime stability at 24 h following continuous infusion was 94.3% +/- 1.0%, which supports the use of continuous infusion.
Anti-Bacterial Agents↗
A wide interindividual variability of urinary 6beta-hydroxycortisol to free cortisol in 487 healthy Japanese subjects in near basal condition.
The frequency distribution of CYP3A activity was investigated by measuring ratios of urinary 6beta-hydroxycortisol to free cortisol in 487 healthy subjects to determine whether a genetic polymorphism for this cytochrome enzyme exists in "native-born" Japanese persons. Spot urine samples (from 9:00 am to 12:00 pm) were collected for measurement of 6beta-hydroxycortisol and free cortisol by high-performance liquid chromatography with a CN column after extracting with a solid-phase column (Bond-Elut C18). The frequency distribution of the urinary 6beta-hydroxycortisol to free cortisol was widely distributed among subjects but with no clear bimodality by a probit plot. Furthermore, the frequency distribution assessed on a new normal test variable plot indicated the possible existence of a CYP3A sexual dimorphism. Mean 6beta-hydroxycortisol levels were higher in women (n = 249) than in men (n = 238) by 1.7-fold, and this difference was statistically significant (P < 0.01). These results show that a CYP3A genetic polymorphism in Japanese persons, based on 6beta-hydroxycortisol excretions, likely does not exist, but there appears to be a broad unimodal distribution of enzyme activity in the population.
Adolescent↗
Potential role of macrolide antibiotics in the management of cystic fibrosis lung disease.
Current management of cystic fibrosis (CF) lung disease includes the use of antibiotics, nutritional support, and airway clearance therapies. However, despite recent advances in pharmacologic therapies including DNase and aerosolized tobramycin, deterioration in lung function persists. Recent investigations have shed new light on the pathogenic mechanisms by which establishes itself within the airways of patients with CF and contributes to the progressive decline in lung function. In particular, the presence of biofilms and other virulence mechanisms allow evasion of local host defenses and establishment of a chronic localized inflammatory response resulting in lung damage. Macrolide antibiotics appear to have a promising role in the management of CF lung disease even though they do not exhibit intrinsic antipseudomonal activity. Recent evidence demonstrates that they can disrupt quorum sensing, a cell-to-cell signaling process linked to the formation of biofilms. In addition, they inhibit NF-kappab and AP-1, nuclear factors that control the expression of proinflammatory cytokines. Their ability to decrease sputum viscosity and increase sputum clearance may complement existing airway clearance therapies. Preliminary clinical trials have shown modest improvement in pulmonary function.
Anti-Bacterial Agents↗