title: Population pharmacokinetic analysis of patritumab, a HER3 inhibitor, in subjects with advanced non-small cell lung cancer (NSCLC) or solid tumors.
abstract: The purpose of this analysis was to develop a population pharmacokinetic (PK) model for patritumab, a fully human monoclonal antibody that targets human epidermal growth factor receptor 3.
  
  
  
  A total of 833 serum concentrations were included in this analysis; serum concentrations were obtained from 145 subjects (136 with non-small cell lung cancer, nine with solid tumors) treated with patritumab [9 or 18 mg/kg intravenously every 3 weeks (q3w)] in one phase 1 and one phase 1b/2 study. Data were analyzed by nonlinear mixed-effect modeling.
  
  
  
  Patritumab PKs were best described through a two-compartment model with first-order elimination and interindividual variability on clearance (CL), volume of the central compartment (V c), distributional clearance, and volume of the peripheral compartment. In the final model, CL and V c were estimated as 0.0238 L/h and 3.62 L, respectively. Body weight (BW) and baseline albumin were found to be covariates for CL and BW was a covariate for V c. Covariates associated with hepatic and renal impairment were not significant on CL. Simulations showed that BW-based dosing reduced interindividual variability in patritumab exposure compared with fixed dosing.
  
  
  
  The PK of patritumab was linear at the doses studied and well described by the two-compartment model. Hepatic and renal impairment did not appear to affect PK. Our results support BW-based dosing of patritumab on a q3w schedule.
authors.affiliation: Translational Medicine and Clinical Pharmacology, Daiichi Sankyo Co., Ltd, 1-2-58, Hiromachi, Shinagawa, Tokyo, 140-8710, Japan. yoshiba.satoshi.s8@daiichisankyo.co.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshiba
authors.affiliation: Translational Medicine and Clinical Pharmacology, Daiichi Sankyo Development, Ltd, Gerrards Cross, UK.
authors.forename: Mendel
authors.initials: M
authors.lastname: Jansen
authors.affiliation: Translational Medicine and Clinical Pharmacology, Daiichi Sankyo Co., Ltd, 1-2-58, Hiromachi, Shinagawa, Tokyo, 140-8710, Japan.
authors.forename: Nobuko
authors.initials: N
authors.lastname: Matsushima
authors.affiliation: Biostatistics and Data Management, Daiichi Sankyo Pharma Development, Edison, NJ, USA.
authors.forename: Shuquan
authors.initials: S
authors.lastname: Chen
authors.affiliation: Translational Medicine and Clinical Pharmacology, Daiichi Sankyo Pharma Development, Edison, NJ, USA.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Mendell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000080908:Broadly Neutralizing Antibodies; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D020893:Receptor, ErbB-3 / Q000037:antagonists & inhibitors*; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D000970:Antineoplastic Agents; D000080908:Broadly Neutralizing Antibodies; C585471:patritumab; C581292:ERBB3 protein, human; D020893:Receptor, ErbB-3
keywords: Modeling; Non-small cell lung cancer; Patritumab; Population pharmacokinetics