title: Population Pharmacokinetic Modelling of FE 999049, a Recombinant Human Follicle-Stimulating Hormone, in Healthy Women After Single Ascending Doses.
abstract: OBJECTIVE
  The purpose of this analysis was to develop a population pharmacokinetic model for a novel recombinant human follicle-stimulating hormone (FSH) (FE 999049) expressed from a human cell line of foetal retinal origin (PER.C6(®)) developed for controlled ovarian stimulation prior to assisted reproductive technologies.
  
  
  METHODS
  Serum FSH levels were measured following a single subcutaneous FE 999049 injection of 37.5, 75, 150, 225 or 450 IU in 27 pituitary-suppressed healthy female subjects participating in this first-in-human single ascending dose trial. Data was analysed by nonlinear mixed effects population pharmacokinetic modelling in NONMEM 7.2.0.
  
  
  RESULTS
  A one-compartment model with first-order absorption and elimination rates was found to best describe the data. A transit model was introduced to describe a delay in the absorption process. The apparent clearance (CL/F) and apparent volume of distribution (V/F) estimates were found to increase with body weight. Body weight was included as an allometrically scaled covariate with a power exponent of 0.75 for CL/F and 1 for V/F.
  
  
  CONCLUSIONS
  The single-dose pharmacokinetics of FE 999049 were adequately described by a population pharmacokinetic model. The average drug concentration at steady state is expected to be reduced with increasing body weight.
authors.affiliation: Experimental Medicine, Ferring Pharmaceuticals A/S, Kay Fiskers Plads 11, 2300, Copenhagen S, Denmark. trinehrose@gmail.com.|Department of Science, Systems, and Models, Roskilde University, 4000, Roskilde, Denmark. trinehrose@gmail.com.
authors.forename: Trine Høyer
authors.initials: TH
authors.lastname: Rose
authors.affiliation: Experimental Medicine, Ferring Pharmaceuticals A/S, Kay Fiskers Plads 11, 2300, Copenhagen S, Denmark.
authors.forename: Daniel
authors.initials: D
authors.lastname: Röshammar
authors.affiliation: Experimental Medicine, Ferring Pharmaceuticals A/S, Kay Fiskers Plads 11, 2300, Copenhagen S, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Erichsen
authors.affiliation: Experimental Medicine, Ferring Pharmaceuticals A/S, Kay Fiskers Plads 11, 2300, Copenhagen S, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Grundemar
authors.affiliation: Department of Science, Systems, and Models, Roskilde University, 4000, Roskilde, Denmark.
authors.forename: Johnny T
authors.initials: JT
authors.lastname: Ottesen
mesh_terms: D000328:Adult; D019540:Area Under Curve; D003277:Contraceptives, Oral, Combined; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D043373:Follicle Stimulating Hormone, Human / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007118:Immunoassay; D010062:Ovulation Induction; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003277:Contraceptives, Oral, Combined; C000608977:FE 999049; D043373:Follicle Stimulating Hormone, Human; D011994:Recombinant Proteins