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New Dosing Regimens (new + dosing_regimen)
Selected AbstractsTwo-Year Results of Once-Weekly Administration of Alendronate 70 mg for the Treatment of Postmenopausal OsteoporosisJOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2002R Rizzoli Abstract The aim of this study was to provide confirmation that once-weekly dosing with 70 mg of alendronate (seven times the daily oral dose) and twice-weekly dosing with 35 mg is equivalent to the 10-mg once-daily regimen and to gain more extensive safety experience with this new dosing regimen. Twelve hundred fifty-eight postmenopausal women (aged 42,95 years) with osteoporosis (bone mineral density [BMD] of either lumbar spine or femoral neck at least 2.5 SDs below peak young adult mean or prior vertebral or hip fracture) were assigned to receive oral once-weekly alendronate, 70 mg (n = 519); twice-weekly alendronate, 35 mg (n = 369); or daily alendronate 10 mg (n = 370) for a total of 2 years of double-blind experience. Mean BMD increases from baseline (95% CI) at 24 months in the once-weekly, twice-weekly, and daily treatment groups, respectively, were 6.8% (6.4, 7.3), 7.0% (6.6, 7.5), and 7.4% (6.9, 7.8) at the lumbar spine and 4.1% (3.8, 4.5), 4.3% (3.9, 4.7), and 4.3% (3.9, 4.7) at the total hip. These increases in BMD as well as the BMD increases at the femoral neck, trochanter, and total body and the reductions of biochemical markers of bone resorption (urinary cross-linked N-telopeptides of type I collagen [NTx]) and bone formation (serum bone-specific alkaline phosphatase [BSAP]) were similar for the three dosing regimens. All treatment regimens were well tolerated with a similar incidence of upper gastrointestinal (GI) adverse experiences. The incidence rates of clinical fractures, captured as adverse experiences, were similar among the groups. The 2-year results confirm the conclusion reached after 1 year that once-weekly alendronate is therapeutically equivalent to daily dosing, providing patients with a more convenient dosing option that may potentially enhance adherence to therapy. [source] Review article: new drug formulations, chemical entities and therapeutic approaches for the management of ulcerative colitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2008S. C. NG Summary Background, Treatment options for ulcerative colitis (UC) are expanding with the development of novel drug formulations and dosing regimens and new chemical entities. Although the goals of medical therapy for UC remain unchanged, that is to induce and to maintain remission, focus has also centred on improving patient compliance, modifying the natural course of disease and healing the mucosa. Aim, To examine novel formulations, new chemical entities and novel therapeutic approaches to the management of UC. Methods, Searches for all studies related to UC treatment in Medline and abstracts from major national and international meetings published in the last 10 years. Results, 5-Aminosalicylic acids (5-ASA) remain the standard first-line treatment for patients with mild to moderately active UC. New formulations with altered delivery, and new dosing regimens have demonstrated possible improvements in efficacy compared with historically available preparations and dosing patterns. Once-daily dosing, micropellet formulations, and high-dose tablets offer enhanced efficacy and improved compliance. 5-ASA is now recognized as a ligand for peroxisome proliferator-activated receptor-, (PPAR-,) and it has a role as a chemo-preventive agent in long-standing UC. New colonic release corticosteroid formulations help to limit systemic toxicity; turmeric, tacrolimus and infliximab have shown promising results. New anti-inflammatory targeted therapies include an anti-CD3 antibody, selective integrin blockers, anti-IL-2 antibody and PPAR-, agonists. Conclusion, The evolution of novel oral 5-ASA formulations and dosage regimens, and recent development of new molecules have expanded the therapeutic armamentarium of UC. [source] Development of a drug,disease simulation model for rituximab in follicular non-Hodgkin's lymphomaBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 4 2009David Ternant WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Serum concentrations of rituximab influence its clinical efficacy in follicular lymphoma (FL), but its concentration,effect relationship has not been described by pharmacokinetic,pharmacodynamic (PK,PD) modelling. , The genetic polymorphism of FCGR3A influences rituximab efficacy and its in vitro concentration,effect relationship. , Increasing rituximab dose and/or number of infusions may lead to a better clinical response in FL. WHAT THIS PAPER ADDS , This study is the first to describe the concentration,effect relationship of rituximab in populations of FL patients. , This PK,PD model relates progression-free survival with rituximab concentrations and takes into account the influence of FCGR3A polymorphism. , Clinical trials testing new dosing regimens of rituximab can be designed using this PK,PD model. AIM Rituximab has dramatically improved the survival of patients with non-Hodgkin's lymphomas (NHL), but the dosing regimen currently used should be optimized. However, the concentration,effect relationship of rituximab has never been described by pharmacokinetic,pharmacodynamic (PK,PD) modelling, precluding the simulation of new dosing regimens. The aim of this study was to develop a PK,PD model of rituximab in relapsed/resistant follicular NHL (FL). METHODS A model describing the relationship between rituximab concentrations and progression-free survival (PFS) was developed using data extracted from the pivotal study, which evaluated 151 relapsed/resistant FL patients. The influence of FCGR3A genetic polymorphism on the efficacy of rituximab was quantified using data from 87 relapsed/resistant FL patients. The predictive performance of the model was analysed using two independent datasets: a study that evaluated rituximab combined with chemotherapy [rituximab, cyclophosphamide, vincristine, adriamycin and prednisone (R-CHOP)] in 334 relapsed/resistant FL patients and a study that evaluated rituximab monotherapy in 47 asymptomatic FL patients with known FCGR3A genotype. RESULTS For R-CHOP, observed and model-predicted PFS (90% confidence interval) at 24 months were 0.50 and 0.48 (0.40, 0.56), respectively, for the observation arm, and 0.62 and 0.59 (0.50, 0.65), respectively, for the rituximab maintenance arm. For rituximab monotherapy, observed and predicted PFS at 24 months were 0.67 and 0.63, respectively, for FCGR3A -V/V patients, and 0.41 and 0.36 (0.25, 0.49), respectively, for FCGR3A -F carriers. CONCLUSIONS Our model provides a satisfactory prediction of PFS at 24 months. It can be used to simulate new dosing regimens of rituximab in populations of FL patients and should improve the design of future clinical trials. [source] | ||||||||||