Population pharmacokinetics of the humanised monoclonal antibody, HuHMFG1 (AS1402), derived from a phase I study on breast cancer

Autor: Xavier Pivot, C Villanueva, W Yin, Mark D. Pegram, Fredrik Erlandsson, Nuhad K. Ibrahim, D Mir, B Royer
Přispěvatelé: Service de Pharmacologie, toxicologie et pharmacovigilance [CHU Limoges], CHU Limoges, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Antisoma Research Limited, University of Miami Leonard M. Miller School of Medicine (UMMSM), MD Anderson Cancer Center [Houston], The University of Texas Health Science Center at Houston (UTHealth), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Saas, Philippe, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Cancer Research
030226 pharmacology & pharmacy
MESH: Antibodies
Monoclonal
0302 clinical medicine
antibody
Medicine
MESH: Glycolipids
skin and connective tissue diseases
MESH: Treatment Outcome
MESH: Aged
HuHMFG1
MESH: Middle Aged
biology
Clinical Trials
Phase I as Topic
Antibodies
Monoclonal
Middle Aged
Prognosis
3. Good health
Phase i study
Survival Rate
Treatment Outcome
Oncology
Monoclonal antibody HuHMFG1
030220 oncology & carcinogenesis
[SDV.IMM]Life Sciences [q-bio]/Immunology
Female
Breast disease
Antibody
Adult
MESH: Survival Rate
[SDV.IMM] Life Sciences [q-bio]/Immunology
medicine.drug_class
MESH: Glycoproteins
Breast Neoplasms
AS1402
Monoclonal antibody
Antibodies
Monoclonal
Humanized
Models
Biological
MESH: Prognosis
Sampling Studies
03 medical and health sciences
Breast cancer
breast cancer
Pharmacokinetics
MESH: Sampling Studies
Humans
linear two-compartment
Aged
Glycoproteins
MESH: Humans
business.industry
MESH: Models
Biological
Cancer
MESH: Adult
Lipid Droplets
medicine.disease
MESH: Clinical Trials
Phase I as Topic
Immunology
Cancer research
biology.protein
population pharmacokinetic
Glycolipids
business
Translational Therapeutics
MESH: Female
MESH: Breast Neoplasms
Zdroj: British Journal of Cancer
British Journal of Cancer, Cancer Research UK, 2010, 102 (5), pp.827-32. ⟨10.1038/sj.bjc.6605560⟩
ISSN: 1532-1827
0007-0920
DOI: 10.1038/sj.bjc.6605560⟩
Popis: International audience; BACKGROUND: HuHMFG1 (AS1402) is a humanised monoclonal antibody that has undergone a phase I trial in metastatic breast cancer. The aim of this study was to characterise the pharmacokinetics (PKs) of HuHMFG1 using a population PK model. METHOD: Data were derived from a phase I study of 26 patients receiving HuHMFG1 at doses ranging from 1 to 16 mg kg(-1). Data were analysed using NONMEM software and covariates were included. A limited sampling strategy (LSS) was developed using training and a validation data set. RESULTS: A linear two-compartment model was shown to be adequate to describe data. Covariate analysis indicated that weight was not related to clearance. An LSS was successfully developed on the basis of the model, in which one sample is collected immediately before the start of an infusion and the second is taken at the end of infusion. CONCLUSION: A two-compartment population PK model successfully describes HuHMFG1 behaviour. The model suggests using a fixed dose of HuHMFG1, which would simplify dosing. The model could be used to optimise dose level and dosing schedule if more data on the correlation between exposure and efficacy become available from future studies. The derived LSS could optimise further PK assessment of this antibody.
Databáze: OpenAIRE
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