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Dosing Strategies (dosing + strategy)
Selected AbstractsTrace Metals in Anaerobic Granular Sludge Reactors: Bioavailability and Dosing StrategiesENGINEERING IN LIFE SCIENCES (ELECTRONIC), Issue 3 2006H. Zandvoort Abstract The trace metal dynamics in anaerobic granular sludge bed reactors and their influence on reactor performance is reviewed in this paper. An insight into the metal dynamics is required from a practical point of view in order to be able to early recognize limitations for essential trace elements, viz., to know when dosing of these elements is required in full-scale anaerobic bioreactor applications. Further such knowledge is indispensable for a rational dosage of these metals, e.g., to ensure maximum substrate conversion rates and to prevent disturbances in reactor performance using a minimum amount of metals. Therefore, the retention, accumulation and release of trace metals in anaerobic granular sludge and the factors affecting these processes need to be known. [source] Aminoglycoside dosing in diabetesJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 2 2000Axworthy Studies have evaluated the comparative efficacy, toxicity and costs associated with extended-interval vs. standard multiple daily dosing of aminoglycosides. In this case, an elderly man with diabetes and good renal function at baseline was switched from standard to extended-interval dosing. During the course of therapy there was evidence of decreased renal function. Pertinent literature was searched for, uncovered and critically evaluated to determine if and what evidence supports using extended dosing of aminoglycosides in this population. No data were found specifically evaluating the different dosing strategies in diabetic patients. However, there were many trials and several meta-analysis located that compared the two dosing strategies, most suggesting at least a cost advantage and possibly less toxicity with extended-interval dosing. Further information is needed to determine whether there is a differential risk for toxicity between these dosing regimens in patient with diabetes. [source] A concise update on the status of liver transplantation for hepatitis B virus: The challenges in 2002LIVER TRANSPLANTATION, Issue 1 2002Hugo E. Vargas Significant improvements in both patient and graft survival after orthotopic liver transplantation (OLT) for hepatitis B virus (HBV)-related liver failure have been made during the last decade. Recurrence of HBV infection has decreased, even in high-risk patients. Despite ongoing progress, challenges remain for the next millennium, including the determination of cost-effective dosing strategies, treatment of HBV infection in liver transplant recipients, and ramifications of the use of new antiviral agents, specifically, the appearance of resistant strains. This review summarizes the relevant history of OLT for chronic viral hepatitis B, details accepted preventive and therapeutic treatments, and discusses ongoing experimental trials. Emphasis also is placed on new approaches in transplantation as they impact on the care of HBV-infected patients. [source] The impact of anterior cruciate ligament injury on lubricin metabolism and the effect of inhibiting tumor necrosis factor , on chondroprotection in an animal modelARTHRITIS & RHEUMATISM, Issue 10 2009K. A. Elsaid Objective To examine the effects of anterior cruciate ligament transection (ACLT) in a rat model on lubricin metabolism and its relationship to markers of inflammation and cartilage damage, and to determine whether blocking the metabolic effects of tumor necrosis factor , (TNF,) by etanercept increases the chondroprotection provided by lubricin. Methods Unilateral ACLT was performed in Lewis rats. Levels of lubricin, TNF,, interleukin-1, (IL-1,), and sulfated glycosaminoglycans (sGAG) in synovial fluid (SF) lavage specimens and synovial tissue lubricin gene expression were evaluated at 1 week and 4 weeks following ACLT. Histologic evaluation of articular cartilage included staining with lubricin-specific monoclonal antibody 9G3 and Safranin O. The percentage of lubricin staining on the surface of articular cartilage in weight-bearing areas was estimated by digital imaging. Blocking of TNF, was performed using etanercept, which was administered subcutaneously at a dose of 0.5 mg/kg around the ACL-transected joints, using different dosing strategies. The ACL-transected and contralateral joints of these rats were harvested 4 weeks following surgery. Results Four weeks following ACLT, SF lubricin concentrations and the percentage of cartilage surface lubricin staining were significantly lower in the injured joints compared with the contralateral joints. A significant decrease in synovial tissue lubricin gene expression was associated with elevated TNF, and IL-1, concentrations in SF lavage samples. With all of the etanercept treatment strategies, blocking of TNF, significantly increased the amount of lubricin bound to cartilage, coupled with a significant decrease in sGAG release. However, changes in the concentrations of lubricin in SF were variable. Conclusion Blocking TNF, resulted in a chondroprotective effect, exemplified by increased lubricin deposition on articular cartilage and a decrease in sGAG release from articular cartilage in an animal model of posttraumatic arthritis. [source] Population pharmacokinetics of mycophenolic acid in children and young people undergoing blood or marrow and solid organ transplantationBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 4 2010Lihua Zeng WHAT IS ALREADY KNOWN ABOUT THIS PROJECT? , Mycophenolate mofetil (MMF) is an immunosuppressant drug used for the treatment and prevention of graft vs. host disease in blood or marrow transplantation and acute graft rejection in solid organ transplantation. , Mycophenolic acid (MPA) pharmacokinetics have not been thoroughly studied in paediatric blood or marrow transplant recipients and guidance for optimal dosing of mycophenolic acid in children is lacking. , Mycophenolic acid exhibits considerable inter- and intra-patient pharmacokinetic variability in adults and paediatric transplant recipients. , The AUC of mycophenolic acid over a 12 h dose interval at steady-state is generally agreed to be the most reliable metric associated with the risk of acute rejection. , Population pharmacokinetic analysis can utilize concentration information from both intensive sampling and sparse sampling to provide pharmacokinetic parameter estimates, estimates of inter- individual and intra-individual variability in these parameters and allows patient characteristics explaining inter-individual variability to be quantified. WHAT THIS STUDY ADDS , This study is one of the first investigations in which a population pharmacokinetic modelling approach was applied to assess the pharmacokinetics of both intravenous and oral MMF in children and young people undergoing blood or marrow and solid organ transplantation. , Bodyweight and concomitant ciclosporin were found to influence MPA pharmacokinetics. , This study evaluated current dosing strategies and found that they may be suboptimal for children weighing less than 10 kg. AIMS To characterize the population pharmacokinetics of mycophenolic acid (MPA) and evaluate dose regimens using a simulation approach and accepted therapeutic drug monitoring targets in children and young people undergoing blood or marrow, kidney and liver transplantation. METHODS MPA concentration,time data were collected using an age specific sampling protocol over 12 h. Some patients provided randomly timed but accurately recorded blood samples. Total and unbound MPA were measured by HPLC. NONMEM was employed to analyze MPA pharmacokinetic data. Simulations (n= 1000) were conducted to assess the suitability of the MPA dose regimens to maintain total MPA AUC(0,12 h) within the range 30 and 60 mg l,1 h associated with optimal outcome. RESULTS A two-compartment pharmacokinetic model with first-order elimination best described MPA concentration,time data. Population mean estimates of MPA clearance, inter-compartmental clearance, volumes of distribution in the central and peripheral compartments, absorption rate constant and bioavailability were 6.42 l h,1, 3.74 l h,1, 7.24 l, 16.8 l, 0.39 h,1 and 0.48, respectively. Inclusion of bodyweight and concomitant ciclosporin reduced the inter-individual variability in CL from 54.3% to 31.6%. Children with a bodyweight of 10 kg receiving standard MPA dose regimens achieve an MPA AUC below the target range suggesting they may be at a greater risk of acute rejection. CONCLUSIONS The population pharmacokinetic model for MPA can be used to explore dosing guidelines for safe and effective immunotherapy in children and young people undergoing transplantation. [source] Phase II study of arsenic trioxide and ascorbic acid for relapsed or refractory lymphoid malignancies: a Wisconsin Oncology Network study,HEMATOLOGICAL ONCOLOGY, Issue 1 2009JE Chang Abstract Arsenic trioxide (As2O3) has established clinical activity in acute promyelocytic leukaemia and has pre-clinical data suggesting activity in lymphoid malignancies. Cell death from As2O3 may be the result of oxidative stress. Agents which deplete intracellular glutathione, such as ascorbic acid (AA), may potentiate arsenic-mediated apoptosis. This multi-institution phase II study investigated a novel dosing schedule of As2O3 and AA in patients with relapsed or refractory lymphoid malignancies. Patients received As2O3 0.25,mg/kg IV and AA 1000,mg IV for five consecutive days during the first week of each cycle followed by twice weekly infusions during weeks 2,6. Cycles were repeated every 8 weeks. The primary end point was objective response. In a subset of patients, sequential levels of intracellular glutathione and measures of Bcl-2 and Bax gene expression were evaluated in peripheral blood mononuclear cells during treatment. Seventeen patients were enrolled between March 2002 and February 2004. The median age was 71, and the majority of enrolled patients had non-Hodgkin's lymphoma (12/17). Sixteen patients were evaluable, and one patient with mantle cell lymphoma achieved an unconfirmed complete response after five cycles of therapy for an overall response rate of 6%. The trial, which had been designed as a two-stage study, was closed after the first stage analysis due to lack of activity. Haematologic toxicities were the most commonly reported events in this heavily pre-treated population, and comprised the majority of grade 3 and 4 toxicities. Intracellular depletion of glutathione was not consistently observed during treatment. As2O3 and AA in this novel dosing strategy was generally well tolerated but had limited activity in patients with relapsed and refractory lymphoid malignancies. Copyright © 2008 John Wiley & Sons, Ltd. [source] Once-daily nevirapine dosing: a pharmacokinetics, efficacy and safety reviewHIV MEDICINE, Issue 1 2007CL Cooper In the context of attempts to simplify treatment regimens and enhance adherence, there is great interest in once-daily dosing regimens for the treatment of HIV-1 infection. Nevirapine has a long half-life and achieves high steady-state plasma concentrations relative to the concentration required to inhibit 50% viral replication in vitro (IC50) in patients. For this reason, it has been considered as a once-daily antiretroviral. Pharmacokinetic and efficacy data support the use of this dosing approach, but excess rash and lingering concerns over liver toxicity preclude use of once-daily dosed nevirapine at this time. Tolerance to high nevirapine concentrations may develop when dose escalation is used during initiation of therapy. It is theoretically possible that the benefits of once-daily dosing may be achieved without excess toxicity by switching to once-daily nevirapine following several months of twice-daily administration. This dosing strategy is currently under evaluation. [source] | ||||||||||