title: Population pharmacokinetics of farletuzumab, a humanized monoclonal antibody against folate receptor alpha, in epithelial ovarian cancer.
abstract: OBJECTIVE
  The purpose of this analysis was to develop a population pharmacokinetic model for farletuzumab, a humanized immunoglobulin (Ig)G(1) monoclonal antibody (mAb) to the folate receptor alpha, which is a receptor over-expressed in ovarian cancer, but largely absent from normal tissue.
  
  
  METHODS
  In total, 2,472 samples were included in the building of the pharmacokinetic model. Farletuzumab 12.5-400 mg/m(2) had been administered via intravenous infusion to 79 patients with advanced ovarian cancer enrolled in one of the two clinical studies. Data were analyzed by a nonlinear mixed-effects modeling approach.
  
  
  RESULTS
  Farletuzumab pharmacokinetics was best described by a two-compartment model with first-order (linear) elimination. In the final model, estimated values of clearance and volume of distribution of the central compartment were 0.00784 l/h and 3.00 l, respectively. Body weight was the only covariate investigated that explained inter-patient variability in clearance and the central volume of distribution. There was no effect of age, human anti-human antibodies, or concomitant chemotherapy on the pharmacokinetics of farletuzumab. Simulations showed that, when the mg/kg/week dose was maintained, steady-state exposure to farletuzumab was similar with dosing every week or every 3 weeks.
  
  
  CONCLUSIONS
  The pharmacokinetic parameters of farletuzumab are similar to those of other IgG mAbs. The results support weight-based dosing of farletuzumab on a weekly or 3-weekly schedule.
authors.affiliation: ICON Clinical Research, Ellicott, MD, USA.
authors.forename: Colm
authors.initials: C
authors.lastname: Farrell
authors.forename: Charles
authors.initials: C
authors.lastname: Schweizer
authors.forename: Jason
authors.initials: J
authors.lastname: Wustner
authors.forename: Susan
authors.initials: S
authors.lastname: Weil
authors.forename: Masayuki
authors.initials: M
authors.lastname: Namiki
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Nakano
authors.forename: Kenya
authors.initials: K
authors.lastname: Nakai
authors.forename: Martin D
authors.initials: MD
authors.lastname: Phillips
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001835:Body Weight; D000077216:Carcinoma, Ovarian Epithelial; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D058975:Folate Receptor 1 / Q000037:antagonists & inhibitors; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D008954:Models, Biological; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000473:pathology; D017711:Nonlinear Dynamics; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014018:Tissue Distribution
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D058975:Folate Receptor 1; C527484:farletuzumab