ArticleInvestigational new drugs2004
Population pharmacokinetics of sibrotuzumab, a novel therapeutic monoclonal antibody, in cancer patients.
Article in Investigational new drugs, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Are population pharmacokinetic and/or pharmacodynamic models adequately evaluated? A survey of the literature from 2002 to 2004.Clinical pharmacokinetics · 2007Pooled it
- Semimechanistic Clearance Models of Oncology Biotherapeutics and Impact of Study Design: Cetuximab as a Case Study.CPT: pharmacometrics & systems pharmacology · 2020Trial
- Use of population approach non-linear mixed effects models in the evaluation of biosimilarity of monoclonal antibodies.European journal of clinical pharmacology · 2016Trial
- A Semi-Mechanistic Mathematical Model of Immune Tolerance Induction to Support Preclinical Studies of Human Monoclonal Antibodies in Rats.Pharmaceutics · 2025Article
- Targeting fibroblast activation protein (FAP): advances in CAR-T cell, antibody, and vaccine in cancer immunotherapy.Drug delivery and translational research · 2023Review
- The Potential of Fibroblast Activation Protein-Targeted Imaging as a Biomarker of Cardiac Remodeling and Injury.Current cardiology reports · 2023Review
- Dual-targeted near-infrared photoimmunotherapy for esophageal cancer and cancer-associated fibroblasts in the tumor microenvironment.Scientific reports · 2022Article
- Fibroblast Activation Protein-α as a Target in the Bench-to-Bedside Diagnosis and Treatment of Tumors: A Narrative Review.Frontiers in oncology · 2021Review
- Imaging of Fibroblast Activation Protein Alpha Expression in a Preclinical Mouse Model of Glioma Using Positron Emission Tomography.Molecules (Basel, Switzerland) · 2020Article
- Pharmacokinetics and Clinical Pharmacology of Monoclonal Antibodies in Pediatric Patients.Paediatric drugs · 2020Review
- Fibroblast activation protein α-positive pancreatic stellate cells promote the migration and invasion of pancreatic cancer by CXCL1-mediated Akt phosphorylation.Annals of translational medicine · 2019Article
- Influence of Antigen Mass on the Pharmacokinetics of Therapeutic Antibodies in Humans.Clinical pharmacokinetics · 2019Review
- Population Pharmacokinetics and Exposure-Response Relationship of Intravenous and Subcutaneous Abatacept in Patients With Rheumatoid Arthritis.Journal of clinical pharmacology · 2019Article
- Article
- Impact of altered endogenous IgG on unspecific mAb clearance.Journal of pharmacokinetics and pharmacodynamics · 2017Article
- The application of the fibroblast activation protein α-targeted immunotherapy strategy.Oncotarget · 2016Review
- A hybrid model of tumor-stromal interactions in breast cancer.Bulletin of mathematical biology · 2013Article
- Targeting tumor microenvironment with silibinin: promise and potential for a translational cancer chemopreventive strategy.Current cancer drug targets · 2013Review
- Anti-neuropilin-1 (MNRP1685A): unexpected pharmacokinetic differences across species, from preclinical models to humans.Pharmaceutical research · 2012Article
- Predicting the F(ab)-mediated effect of monoclonal antibodies in vivo by combining cell-level kinetic and pharmacokinetic modelling.Journal of pharmacokinetics and pharmacodynamics · 2012Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Population pharmacokinetics of sibrotuzumab, a humanized monoclonal antibody directed against fibroblast activation protein, were determined after multiple intravenous infusions of dosages ranging from 5 mg/m(2) to an absolute dose of 100 mg, in patients with advanced or metastatic carcinoma. In total, 1844 serum concentrations from 60 patients in three Phase I and II clinical studies were analyzed. The structural model incorporated two disposition compartments and two parallel elimination pathways from the central compartment, one linear and one nonlinear. Finally estimated pharmacokinetic parameters (%RSE) were: linear clearance CLL 22.1 ml/h (9.6), central distribution volume V1 4.13l (3.7), peripheral volume V2 3.19l (8.8), inter-compartmental clearance Q 37.6 ml/h (9.6); for the nonlinear clearance Vmax was 0.0338 mg/h (25) and Km 0.219 microg/ml (57). At serum concentrations between approximately 20 ng/ml and 7 microg/ml, the effect of the nonlinear clearance on pharmacokinetics was marked. Only at >7 microg/ml did CLL dominate overall clearance. Interindividual variability was 57% for CLL, 20% for V1 and V2, and 29% for Vmax and was larger than the inter-occasional variability of 13%. Of the many investigated patient covariates, only body weight was found to contribute to the population model. It significantly affected CLL, V1, V2 and Vmax resulting in marked differences in the model-predicted concentration-time profiles after multiple dosing in patients with low and high body weights. In conclusion, a robust population pharmacokinetic model was developed and evaluated for sibrotuzumab, which identified a possible need to consider body weight when designing dosage regimen for future clinical cancer trials.
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Registered trials
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