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Optimal Dosing (optimal + dosing)
Selected AbstractsUse of pharmacokinetics in the coagulation factor treatment of patients with haemophiliaHAEMOPHILIA, Issue 6 2005A. D. Shapiro Summary., Dosing decisions for replacement coagulation factors in patients with haemophilia should be made on an individual patient basis, with the required dose dependent on factors including the clinical situation, the severity of the factor deficiency, and the location and extent of bleeding. Moreover, there is considerable variability in the pharmacokinetics of coagulation products that needs to be considered; in particular, with both factor (F) IX and FVIII products, there is considerable inter-patient variability in in vivo recovery and terminal half-life values. In the present report, we provide a practical guide to calculating and applying pharmacokinetic parameters relevant to the optimal dosing of coagulation products. We discuss the conduct of a pharmacokinetic study in an individual patient, how to calculate pharmacokinetic values from raw data and clinical situations where an individual pharmacokinetic study is helpful. We highlight the importance of considering an individual pharmacokinetic study in all patients starting a new coagulation product. [source] Botulinum Neurotoxin for the Treatment of Migraine and Other Primary Headache Disorders: From Bench to BedsideHEADACHE, Issue 2003David W. Dodick MD Botulinum toxin type A, a neurotoxin, is effective for treating a variety of disorders of involuntary muscle contraction including cervical dystonia, blepharospasm, and hemifacial spasm. It inhibits neuromuscular signaling by blocking the release of acetylcholine at the neuromuscular junction. The biological effects of the toxin are transient, with normal neuronal signaling returning within approximately 3 to 6 months postinjection. Recent clinical findings suggest that botulinum toxin type A may inhibit pain associated with migraine and other types of headache. However, the mechanism by which this toxin inhibits pain is not fully understood and is under investigation. Research findings suggest that botulinum toxin type A inhibits the release of neurotransmitters from nociceptive nerve terminals and, in this way, may possess an analgesic effect. A number of retrospective open-label chart reviews and 3 double-blind, placebo-controlled trials have demonstrated that localized injections of botulinum toxin type A significantly reduce the frequency, severity, and disability associated with migraine headaches. Although the majority of patients in these studies experienced no botulinum toxin type A-mediated side effects, a small percentage of patients did report transient minor side effects including blepharoptosis, diplopia, and injection-site weakness. Currently, 4 randomized, placebo-controlled, clinical trials are being conducted to evaluate the efficacy, optimal dosing, and side-effect profile of botulinum toxin type A as a novel treatment for migraine and other types of headache. These studies may provide further evidence that botulinum toxin type A is an effective option for the preventive treatment of migraine. [source] Pharmacodynamics of warfarin in catsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2000S. A. SMITH The overall purpose of this study was to evaluate the pharmacodynamic response to warfarin in cats. The specific aim was to determine if a log-linear indirect response model (Nagashima et al., 1969) used to describe the in vivo effect of warfarin in humans could be applied to cats. The pharmacokinetics of racemic warfarin were described using a non-compartmental approach. The relationship between prothrombin complex activity (PCA) and normalized prothrombin time (PTR) was defined for feline plasma under our experimental conditions, and determined to be: %PCA=12.38+648 e,PTR/0.492. These data were then integrated and used to predict the warfarin dose associated with therapeutic anti-coagulation defined as an International Normalized Ratio (INR) of 2.0,3.0. The maximum prothrombinopenic response to warfarin in cats after a single intravenous dose of 0.5 mg/kg occurred at 24,48 h. Pharmacodynamic modeling suggested that each cat had a narrow therapeutic range of the steady-state concentration of total warfarin required to appropriately block prothrombin complex synthesis (median: 265.2,358.7 ng/mL). The median daily dose range predicted to yield therapeutic concentrations of warfarin was 0.061,0.088 mg/kg per day. Wide inter-individual variations in both pharmacokinetics and pharmacodynamic response suggest that a more optimal dosing of warfarin may be possible with the development of individual pharmacokinetic/pharmacodynamic algorithms, analogous to those currently employed in human patients. [source] Sustained response with rituximab in patients with thrombotic thrombocytopenic purpura: A report of 13 cases and review of the literature,AMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2009Huichung T. Ling Idiopathic thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease mediated by autoantibodies directed against ADAMTS-13. A number of small series and case reports have shown promising results with rituximab in refractory or relapsed TTP. In this report, we present 13 patients with TTP treated with rituximab. Twelve of the 13 patients (92%) achieved complete response; no subsequent relapses occurred with median follow-up of 24 months (range, 13,84 months). The addition of rituximab to standard therapy appears to be effective in sustaining long-term remission in TTP. However, the optimal dosing and timing of rituximab warrant further investigation. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source] Current and future use of the mannitol bronchial challenge in everyday clinical practiceTHE CLINICAL RESPIRATORY JOURNAL, Issue 4 2009Celeste Porsbjerg Abstract Objectives:, Asthma is a disease associated with inflammation, airway hyperresponsiveness (AHR) and airflow limitation. Clinical diagnosis and management of asthma often relies on assessment of lung function and symptom control, but these factors do not always correlate well with underlying inflammation. Bronchial challenge tests (BCTs) assess AHR, and can be used to assist in the diagnosis and management of asthma. Data Source:, Data presented at the symposium ,Use of inhaled mannitol for assessing airways disease' organised by the Allied Respiratory Professionals Assembly (9) of the European Respiratory Society (ERS) at the ERS Congress, Berlin 2008. Results:, Indirect challenge tests such as exercise testing, hypertonic saline or adenosine 5,-monophosphate (AMP) are more specific though less sensitive than direct challenge tests (such as methacholine) for identifying patients with active asthma. Indirect BCTs may be used to diagnose exercise-induced bronchoconstriction or AHR consistent with active asthma, to evaluate AHR that will respond to treatment with anti-inflammatory drugs and to determine the effectiveness and optimal dosing of such therapy. An ideal indirect challenge test should be standardised and reproducible, and the test result should correlate with the degree of airway inflammation. The mannitol BCT provides a standardised and rapid point-of-need test to identify currently active asthma, and is clinically useful in the identification of patients with asthma who are likely to benefit from inhaled corticosteroid therapy. Conclusion:, In the future, mannitol BCT may be added to lung function and symptom assessment to aid in the everyday management of asthma. Please cite this paper as: Porsbjerg C, Backer V, Joos G, Kerstjens HAM and Rodriguez-Roisin R. Current and future use of the mannitol bronchial challenge in everyday clinical practice. The Clinical Respiratory Journal 2009; 3: 189,197. [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] | ||||||||||