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Population Pharmacokinetic Modelling of FE 999049, a Recombinant Human Follicle-Stimulating Hormone, in Healthy Women After Single Ascending Doses

Rose, Trine Høyer; Röshammar, Daniel; Erichsen, Lars; Grundemar, Lars LU and Ottesen, Johnny T (2016) In Drugs 16(2). p.80-173
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... (More)

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.

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author
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Contribution to journal
publication status
published
subject
keywords
Adult, Area Under Curve, Contraceptives, Oral, Combined, Dose-Response Relationship, Drug, Double-Blind Method, Female, Follicle Stimulating Hormone, Human/administration & dosage, Humans, Immunoassay, Ovulation Induction, Recombinant Proteins/administration & dosage, Treatment Outcome, Young Adult
in
Drugs
volume
16
issue
2
pages
8 pages
publisher
Adis International
ISSN
0012-6667
DOI
10.1007/s40268-016-0129-9
language
English
LU publication?
no
id
718cf8a9-db43-4171-8b49-f37e3ad1545e
date added to LUP
2019-09-03 12:54:46
date last changed
2019-09-04 16:28:35
@article{718cf8a9-db43-4171-8b49-f37e3ad1545e,
  abstract     = {<p>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.</p><p>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.</p><p>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.</p><p>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.</p>},
  author       = {Rose, Trine Høyer and Röshammar, Daniel and Erichsen, Lars and Grundemar, Lars and Ottesen, Johnny T},
  issn         = {0012-6667},
  keyword      = {Adult,Area Under Curve,Contraceptives, Oral, Combined,Dose-Response Relationship, Drug,Double-Blind Method,Female,Follicle Stimulating Hormone, Human/administration & dosage,Humans,Immunoassay,Ovulation Induction,Recombinant Proteins/administration & dosage,Treatment Outcome,Young Adult},
  language     = {eng},
  number       = {2},
  pages        = {80--173},
  publisher    = {Adis International},
  series       = {Drugs},
  title        = {Population Pharmacokinetic Modelling of FE 999049, a Recombinant Human Follicle-Stimulating Hormone, in Healthy Women After Single Ascending Doses},
  url          = {http://dx.doi.org/10.1007/s40268-016-0129-9},
  volume       = {16},
  year         = {2016},
}