Trial reportClinical pharmacokinetics2009
Pharmacokinetics and pharmacodynamics of the erythropoietin Mimetibody construct CNTO 528 in healthy subjects.
Trial report in Clinical pharmacokinetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Live long and active: Polypeptide-mediated assembly of antibody variable fragments.Advanced drug delivery reviews · 2020Pooled it
- A semi-mechanistic population pharmacokinetic-pharmacodynamic model to assess downstream drug-target effects on erythropoiesis.Journal of pharmacokinetics and pharmacodynamics · 2025Trial
- Population pharmacokinetic and pharmacodynamic model-based comparability assessment of a recombinant human Epoetin Alfa and the Biosimilar HX575.Journal of clinical pharmacology · 2012Trial
- Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling for Iron-Regulated Hematopoietic Stem and Progenitor Cells' Commitment toward Erythroid and Megakaryocytic Lineages.ACS pharmacology & translational science · 2025Article
- Novel Combination of Erythropoietin and Romiplostim to Treat Chemotherapy-Induced Anemia and Thrombocytopenia via Pharmacodynamic Interaction on Hematopoietic Stem and Progenitor Cells.ACS pharmacology & translational science · 2023Article
- Exposure-response analyses of efzofitimod in patients with pulmonary sarcoidosis.Frontiers in pharmacology · 2023Article
- A Novel Combination Therapy of Erythropoietin and Thrombopoietin to Treat Erythropoietin-Resistance anemia.Pharmaceutical research · 2022Article
- Delay differential equations based models in NONMEM.Journal of pharmacokinetics and pharmacodynamics · 2021Article
- Delayed logistic indirect response models: realization of oscillating behavior.Journal of pharmacokinetics and pharmacodynamics · 2018Article
- Pharmacodynamic Model of Hepcidin Regulation of Iron Homeostasis in Cynomolgus Monkeys.The AAPS journal · 2016Article
- Targeting EPO and EPO receptor pathways in anemia and dysregulated erythropoiesis.Expert opinion on therapeutic targets · 2016Review
- Management of anemia with erythropoietic-stimulating agents in children with chronic kidney disease.Pediatric nephrology (Berlin, Germany) · 2014Review
- Modeling of delays in PKPD: classical approaches and a tutorial for delay differential equations.Journal of pharmacokinetics and pharmacodynamics · 2014Article
- Clinical pharmacokinetics and pharmacodynamics of erythropoiesis-stimulating agents.Clinical pharmacokinetics · 2013Review
- Pharmacokinetics and pharmacokinetic-pharmacodynamic correlations of therapeutic peptides.Clinical pharmacokinetics · 2013Review
- Fundamentals of population pharmacokinetic modelling: validation methods.Clinical pharmacokinetics · 2012Review
- Lifespan based indirect response models.Journal of pharmacokinetics and pharmacodynamics · 2012Review
- Treatment of anemia in chronic kidney disease: known, unknown, and both.Journal of blood medicine · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveAnaemia is a serious comorbidity that is common in patients with renal failure or cancer. CNTO 528 is the first Mimetibody developed to mimic the effects of erythropoietin (EPO), a hormone that stimulates the production of red blood cells (RBCs). The objective of this study was to develop a pharmacokinetic and pharmacodynamic model for CNTO 528 in healthy male subjects.
methodsA pharmacokinetic/pharmacodynamic model for CNTO 528 was developed to describe the serum concentration versus time profile and the pharmacological responses of percentage of reticulocytes, total RBC counts and haemoglobin concentration after a single intravenous administration of CNTO 528 at 0.03, 0.09, 0.3 and 0.9 mg/kg in 24 healthy subjects. An open, linear, two-compartment model was used to characterize the pharmacokinetic parameters of CNTO 528. A catenary cell production and lifespan loss model was used to fit the pharmacodynamic data, yielding estimates of drug potency (SC(50)), efficacy (S(max)) and other pharmacodynamic parameters. Bootstrap and posterior predictive checks (PPC) were used to evaluate the model.
resultsAdministration of CNTO 528 stimulated the production of reticulocytes, RBCs and haemoglobin. CNTO 528 exhibits a half-life of 141 hours, or approximately 5.9 days. The SC(50) was estimated to be 0.37 mg/L, indicating that low serum CNTO 528 concentration was sufficient to produce pharmacological effects. Compared with historical controls, CNTO 528 S(max) appears to be 2-fold higher than recombinant human EPO. Bootstrap analysis and PPCs confirmed the accuracy and precision in the parameter estimates and the adequacy of the model to describe the CNTO 528 pharmacokinetics and pharmacodynamics.
conclusionThe mechanistic population model was suitable to characterize the pharmacokinetics and pharmacodynamics of intravenously administered CNTO 528 in healthy subjects. This qualified model is deemed appropriate to conduct clinical trial simulations and to support the decision-making process for dose selection in studies of EPO-stimulating agents.
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