title: Pharmacokinetic and pharmacodynamic interactions between recombinant human luteinizing hormone and recombinant human follicle-stimulating hormone.
abstract: OBJECTIVE
  To assess the pharmacokinetics of a recombinant human LH preparation and its pharmacokinetic and pharmacodynamic interactions with recombinant human follicle-stimulating hormone (FSH).
  
  
  METHODS
  Prospective, randomized cross-over study.
  
  
  METHODS
  Phase I clinical research environment.
  
  
  METHODS
  Twelve healthy pituitary down-regulated females.
  
  
  METHODS
  Subjects received 150 IU of s.c. recombinant human LH and FSH, either alone or in combination, followed by recombinant human LH and FSH once daily for 7 days.
  
  
  METHODS
  Pharmacokinetic parameters, ovarian follicle development.
  
  
  RESULTS
  No pharmacokinetic interaction between recombinant human LH and FSH was observed, with no significant difference in baseline-corrected maximal observed concentration over baseline, area under the concentration-time curve from t = 0 to t = 24 hours, or time to maximal concentration after single doses alone or in combination. After daily administration, the mean accumulation ratio was 1.6 for LH and 2.9 for FSH, with absorption and terminal phase half-life estimates of 4 and 11 hours for LH and 8 and 16 hours for FSH, respectively. Combined administration of FSH and LH for 7 days was effective in stimulating ovarian follicular development and steroidogenesis, with large interindividual variability related to ovarian sensitivity.
  
  
  CONCLUSIONS
  A new recombinant human LH preparation has a low accumulation ratio at steady-state and no pharmacokinetic or pharmacodynamic interactions with recombinant human FSH.
authors.affiliation: Serono International S.A., Geneva, Switzerland.
authors.forename: J Y
authors.initials: JY
authors.lastname: le Cotonnec
authors.forename: E
authors.initials: E
authors.lastname: Loumaye
authors.forename: H C
authors.initials: HC
authors.lastname: Porchet
authors.forename: V
authors.initials: V
authors.lastname: Beltrami
authors.forename: A
authors.initials: A
authors.lastname: Munafo
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004338:Drug Combinations; D004958:Estradiol / Q000097:blood / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives; D017273:Goserelin / Q000494:pharmacology; D006207:Half-Life; D006801:Humans; D007265:Inhibins / Q000097:blood / Q000378:metabolism; D007279:Injections, Subcutaneous; D007986:Luteinizing Hormone / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D006080:Ovarian Follicle / Q000187:drug effects; D010902:Pituitary Gland / Q000187:drug effects; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D013997:Time Factors
chemical_list: D004338:Drug Combinations; D011994:Recombinant Proteins; D017273:Goserelin; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007265:Inhibins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone