title: Population pharmacokinetics of the humanised monoclonal antibody, HuHMFG1 (AS1402), derived from a phase I study on breast cancer.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: CHU Besançon, Laboratoire de Pharmacologie Clinique, Hôpital Jean Minjoz, Besançon, France. broyer@chu-besancon.fr
authors.forename: B
authors.initials: B
authors.lastname: Royer
authors.forename: W
authors.initials: W
authors.lastname: Yin
authors.forename: M
authors.initials: M
authors.lastname: Pegram
authors.forename: N
authors.initials: N
authors.lastname: Ibrahim
authors.forename: C
authors.initials: C
authors.lastname: Villanueva
authors.forename: D
authors.initials: D
authors.lastname: Mir
authors.forename: F
authors.initials: F
authors.lastname: Erlandsson
authors.forename: X
authors.initials: X
authors.lastname: Pivot
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D001943:Breast Neoplasms / Q000378:metabolism*; D017321:Clinical Trials, Phase I as Topic; D005260:Female; D006017:Glycolipids / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D066292:Lipid Droplets; D008875:Middle Aged; D008954:Models, Biological; D011379:Prognosis; D012494:Sampling Studies; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D006017:Glycolipids; D006023:Glycoproteins; C110367:milk fat globule; C547393:epitumomab