Quantitative assessment of minimal effective concentration of erythropoiesis-stimulating agents
نویسندگان
چکیده
Minimal effective concentration (MEC) was proposed to explain why subcutaneous (SC) administration of erythropoietin (EPO) induces a higher hemoglobin (HGB) increase than intravenous (IV) administration. It has been further used to explain the paradox that erythropoiesis-stimulating agent (ESA) with lower receptor binding affinity may have higher in vivo activity. We have developed a pharmacokinetic and pharmacodynamic (PK/PD) model with incorporation of the operational model of agonism to characterize the data from two clinical trials. By using model-based simulations, we demonstrate that SC route is more efficacious than IV route and explain the paradoxical behavior of ESAs. We determined that MEC can be quantified by C50, which represents the concentration of an ESA producing its half-maximal effect of stimulating the proliferation of erythroid precursor cells. The model used may allow joint PK/PD modeling of data from different ESAs, and provide a platform for dosing regimen optimizations and future clinical study designs.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e62; doi:10.1038/psp.2013.39; published online 7 August 2013.
منابع مشابه
Patient and physician characteristics associated with erythropoiesis-stimulating agent use in patients with myelodysplastic syndromes.
Patient and physician characteristics associated with use of erythropoiesis-stimulating agents in myelodysplastic syndrome patients have not yet been described. Myelodysplastic syndrome patients diagnosed from 2001 to 2005 were identified from the Surveillance Epidemiology and End Results-Medicare database. Multivariate regressions examined the association between patient and physician characte...
متن کاملThe Prevalence and Management of Anemia in Chronic Kidney Disease Patients: Result from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD)
Anemia is a common and significant complication of chronic kidney disease (CKD). However, its prevalence and current management status has not been studied thoroughly in Korea. We examined the prevalence of anemia, its association with clinical and laboratory factors, and utilization of iron agents and erythropoiesis stimulating agents using the baseline data from the large-scale CKD cohort in ...
متن کاملThe role of erythropoietin (EPO) and erythropoiesis stimulating agents (ESAs) in tumor progression
متن کامل
Benefits and harms of erythropoiesis-stimulating agents for anemia related to cancer: a meta-analysis.
BACKGROUND Erythropoiesis-stimulating agents are used to treat anemia in patients with cancer. However, their safety and effectiveness is controversial. We did a systematic review of the clinical efficacy and harms of these agents in adults with anemia related to cancer or chemotherapy. METHODS We conducted a systematic review of published and unpublished randomized controlled trials (RCTs) u...
متن کاملBiomarkers for Assessing and Managing Iron Deficiency Anemia in Late-Stage Chronic Kidney Disease Executive Summary
Chronic kidney disease (CKD) is the gradual, progressive deterioration of kidney function, and a condition that affects an estimated 26 million American adults. A common complication of CKD is anemia, which results from inadequate erythropoietin or from iron deficiency as a result of inadequate absorption or mobilization. The management of anemia in CKD patients must strike an appropriate balan...
متن کامل