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Toxicity associated with Refugio Beach front Acrylic to be able to Sand Crabs (Emerita analoga), Azure Mussels (Mytilus sp.), along with National Silversides (Menidia beryllina).
BACKGROUND Critically ill patients show several pathophysiological alterations that can complicate antibiotic dosing. Hence, there is a strong rationale to individualize anti-infective dosing in these patients by utilizing therapeutic drug monitoring (TDM). The current study aimed to develop and validate a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of total and unbound plasma concentrations of three commonly used antibiotics (meropenem, imipenem/cilastatin, and cefoperazone/sulbactam) in the treatment of infections in critically ill patients in China, which could be suitable for routine TDM in hospital laboratories. METHODS The unbound drug was separated from the bound drug by ultrafiltration. Simple protein precipitation was used for sample preparation. Meropenem, imipenem/cilastatin, cefoperazone/sulbactam, and their corresponding internal standards were then resolved using the Waters CORTECS C18 column. All the compounds were detected using electrospray ionization in the positive/negative ion-switching mode. RESULTS The calibration curves were linear for all compounds, with correlation coefficients (R) above 0.99 for total concentrations in human plasma and unbound concentrations in the plasma ultrafiltrate. For both total and unbound drugs, the relative errors and intra/inter-assay relative standard deviations were below 15%. The limit of quantification was 0.05 μg/mL for both total plasma concentrations and plasma ultrafiltrate concentrations of all compounds. CONCLUSIONS The method was simple, rapid, and reliable and is currently being used to provide a TDM service to enhance the efficacious use of the three antibiotics.BACKGROUND The aim of this study was to conduct a population pharmacokinetic (PK) analysis of meropenem and to explore the optimal dosing strategy for meropenem in critically ill patients with acute kidney injury (AKI) receiving treatment with continuous hemodiafiltration (CHDF). METHODS Blood samples were obtained on Days 1, 2, and 5 after the start of meropenem administration, immediately before dosing, and at 1, 2, 6, and 8 h after dosing. Population PK model analysis was performed and concentration-time profiles were simulated by using Nonlinear Mixed Effects Model software. RESULTS Twenty-one patients receiving CHDF in our intensive care unit were enrolled and 350 serum concentration-time data points were obtained. The PK of meropenem were best described using a two-compartment model. Typical total and inter-compartmental clearance values were 4.22 L/h and 7.84 L/h, respectively, whereas the central and peripheral compartment volumes of distribution were 14.82 L and 11.75 L, respectively. Estimated glomerular filtration rate (eGFR) was identified as a significant covariate of meropenem total clearance. In simulations of patients with renal failure receiving CHDF, the dose was affected by eGFR; a dose of 0.5 g every 8 h or 1 g every 12 h showed the probability of target attainment of achieving 100% time above the minimum inhibitory concentration (MIC) for bacteria with an MIC ≤ 2 mg/L. CONCLUSION A population PK model was developed for meropenem in critically ill patients with AKI receiving CHDF. Our results indicated that a meropenem dosage of 0.5 g every 8 h or 1 g every 12 h was suitable in this population and for susceptible bacteria.BACKGROUND In the era of multiple daily dosing of systemic aminoglycosides, a circadian rhythm in the clearance of these vital antibiotics has been demonstrated in animals and healthy volunteers. Over the past decade, once-daily dosing regimens have been proved to be less nephrotoxic and were therefore adopted worldwide for most indications requiring treatment with an aminoglycoside. In this study, the effect of time of administration on the pharmacokinetics of once-daily tobramycin in adults with cystic fibrosis (CF) experiencing a pulmonary exacerbation was investigated. METHODS In this open randomized study, patients with CF received intravenous tobramycin at 800 or 2200 h. Pharmacokinetic and kidney function parameters were compared between the two groups. RESULTS Twenty-five patients were included. The mean weight-corrected clearances of tobramycin were 1.46 vs. 1.43 mL/h*kg (p=0.50) and mean volumes of distribution were 0.25 vs. 0.27 L/kg (p=0.54) for the 800 and 2200 groups, respectively. In addition, no significant differences were detected in changes in estimated clearances of creatinine or tobramycin on day 1 and day 8 in the 800 or 2200 group indicating that there was no decline in clearance over time. At day 8 of therapy, the increase in serum blood urea nitrogen in the 2200 group was significantly higher than that in the 800 group (1.8 vs. 0.2 mmol/L, p=0.015). CONCLUSIONS The time of administration (800 vs 2200) did not affect tobramycin pharmacokinetics in the adult CF population studied. The increase in serum blood urea nitrogen in the 2200 group requires further investigation.Altered pronociceptive and antinociceptive mechanisms are often implicated in painful conditions and have been increasingly studied over the past decade. For some painful conditions, alterations are well-established, but in populations with low back pain (LBP), there remains considerable debate whether these mechanisms are altered. The present systematic review aimed to address this issue by identifying studies assessing conditioned pain modulation (CPM) and/or temporal summation of pain (TSP) in patients with LBP, comparing with either a healthy control group or using a method with reference data available. Qualitative synthesis and quantitative meta-analysis of group differences were performed. For CPM and TSP, 20 and 29 original articles were eligible, with data for meta-analysis obtainable from 18 (1500 patients and 505 controls) and 27 (1507 patients and 1127 controls) studies, respectively. Most studies were of poor-to-fair quality with significant heterogeneity in study size, population, assessment methodology, and outcome. AG825 Nonetheless, CPM was impaired in patients with LBP compared with controls (standardized mean difference = -0.44 [-0.64 to -0.23], P less then 0.001), and the magnitude of this impairment was related to pain chronicity (acute/recurrent vs chronic, P = 0.003), duration (RS = -0.62, P = 0.006), and severity (RS = -0.54, P = 0.02). Temporal summation of pain was facilitated in patients with LBP compared with controls (standardized mean difference = 0.50 [0.29-0.72], P less then 0.001), and the magnitude of this facilitation was weakly related to pain severity (RS= 0.41, P = 0.04) and appeared to be influenced by test modality (P less then 0.001). Impaired CPM and facilitated TSP were present in patients with LBP compared with controls, although the magnitude of differences was small which may direct future research on the clinical utility.
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