title: Impact of patient characteristics on the pharmacokinetics of corifollitropin alfa during controlled ovarian stimulation.
abstract: The aim of the present study was to characterize the pharmacokinetic profile of corifollitropin alfa and examine the relationships between dose, intrinsic factors [body weight, body mass index (BMI), age and race] and corifollitropin alfa pharmacokinetics.
  
  
  
  Data from five phase II and III clinical trials of corifollitropin alfa were evaluated. All subjects included in the analysis received 60 - 180 μg corifollitropin alfa for controlled ovarian stimulation in a gonadotrophin-releasing hormone antagonist protocol followed by daily recombinant follicle stimulating hormone (rFSH) from day 8 onwards. Serum corifollitropin alfa levels (across the entire range of treatment) and total follicle stimulating hormone immunoreactivity levels (up to the start of rFSH treatment) were indicators of drug exposure. The analyses were performed using a nonlinear mixed-effects modelling approach.
  
  
  
  A total of 2630 subjects were treated with corifollitropin alfa, and 2557 subjects were evaluable for analysis. Body weight, BMI and race (Asian and Black vs. Caucasian) were significant determinants of corifollitropin alfa exposure. Dose-normalized corifollitropin alfa exposure was ~89% higher in women with a body weight of 50 kg vs. 90 kg (in subjects with a similar BMI of 24 kg m(-2) ); 14% higher in women with a BMI of 18 kg m(-2) vs. 32 kg m(-2) (provided they were of similar body weight); and ~15.7% lower in Asian subjects and 13% higher in Black subjects vs. Caucasian subjects.
  
  
  
  Body weight was the major determinant of corifollitropin alfa exposure; BMI and race (Asian and Black) were also determinants but to a lesser extent and without associated effects on clinical outcomes. Corifollitropin alfa dose adjustment is indicated, based on body weight but not for BMI or race. These recommendations are consistent with the product label.
authors.affiliation: MSD BV, Oss, The Netherlands.
authors.forename: Anthe S
authors.initials: AS
authors.lastname: Zandvliet
authors.affiliation: MSD BV, Oss, The Netherlands.
authors.forename: Marita
authors.initials: M
authors.lastname: Prohn
authors.affiliation: MSD BV, Oss, The Netherlands.
authors.forename: Rik
authors.initials: R
authors.lastname: de Greef
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: van Aarle
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: McCrary Sisk
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Stegmann
mesh_terms: D000328:Adult; D015992:Body Mass Index; D001835:Body Weight; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004305:Dose-Response Relationship, Drug; D005260:Female; D043373:Follicle Stimulating Hormone, Human / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D017711:Nonlinear Dynamics; D010062:Ovulation Induction / Q000379:methods*; D044469:Racial Groups
chemical_list: D043373:Follicle Stimulating Hormone, Human; C437186:follicle stimulating hormone, human, with HCG C-terminal peptide
keywords: age; controlled ovarian stimulation; corifollitropin alfa; population pharmacokinetics; race; weight