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

Trine Høyer Rose, Daniel Röshammar, Lars Erichsen, Lars Grundemar, Johnny T. Ottesen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.
OriginalsprogEngelsk
TidsskriftDrugs in R&D
Vol/bind16
Udgave nummer2
Sider (fra-til)173-180
Antal sider8
ISSN1174-5886
DOI
StatusUdgivet - 2016

Citer dette

@article{b292960395754c44b1cf11830554a9bd,
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 apopulation pharmacokinetic model for a novel recombinanthuman follicle-stimulating hormone (FSH) (FE 999049)expressed from a human cell line of foetal retinal origin(PER.C6) developed for controlled ovarian stimulation priorto assisted reproductive technologies.Methods: Serum FSH levels were measured following asingle subcutaneous FE 999049 injection of 37.5, 75, 150,225 or 450 IU in 27 pituitary-suppressed healthy femalesubjects participating in this first-in-human single ascendingdose trial. Data was analysed by nonlinear mixedeffects population pharmacokinetic modelling in NONMEM7.2.0.Results: A one-compartment model with first-orderabsorption and elimination rates was found to best describethe data. A transit model was introduced to describe a delayin the absorption process. The apparent clearance (CL/F)and apparent volume of distribution (V/F) estimates werefound to increase with body weight. Body weight wasincluded as an allometrically scaled covariate with a powerexponent of 0.75 for CL/F and 1 for V/F.Conclusions: The single-dose pharmacokinetics of FE999049 were adequately described by a population pharmacokineticmodel. The average drug concentration at steadystate is expected to be reduced with increasing body weight.",
author = "Rose, {Trine H{\o}yer} and Daniel R{\"o}shammar and Lars Erichsen and Lars Grundemar and Ottesen, {Johnny T.}",
year = "2016",
doi = "10.1007/s40268-016-0129-9",
language = "English",
volume = "16",
pages = "173--180",
journal = "Drugs in R&D",
issn = "1174-5886",
publisher = "Adis International Ltd.",
number = "2",

}

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; Ottesen, Johnny T.

I: Drugs in R&D, Bind 16, Nr. 2, 2016, s. 173-180.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Population Pharmacokinetic Modelling of FE 999049, a Recombinant Human Follicle-Stimulating Hormone, in Healthy Women After Single Ascending Doses

AU - Rose, Trine Høyer

AU - Röshammar, Daniel

AU - Erichsen, Lars

AU - Grundemar, Lars

AU - Ottesen, Johnny T.

PY - 2016

Y1 - 2016

N2 - Objective: The purpose of this analysis was to develop apopulation pharmacokinetic model for a novel recombinanthuman follicle-stimulating hormone (FSH) (FE 999049)expressed from a human cell line of foetal retinal origin(PER.C6) developed for controlled ovarian stimulation priorto assisted reproductive technologies.Methods: Serum FSH levels were measured following asingle subcutaneous FE 999049 injection of 37.5, 75, 150,225 or 450 IU in 27 pituitary-suppressed healthy femalesubjects participating in this first-in-human single ascendingdose trial. Data was analysed by nonlinear mixedeffects population pharmacokinetic modelling in NONMEM7.2.0.Results: A one-compartment model with first-orderabsorption and elimination rates was found to best describethe data. A transit model was introduced to describe a delayin the absorption process. The apparent clearance (CL/F)and apparent volume of distribution (V/F) estimates werefound to increase with body weight. Body weight wasincluded as an allometrically scaled covariate with a powerexponent of 0.75 for CL/F and 1 for V/F.Conclusions: The single-dose pharmacokinetics of FE999049 were adequately described by a population pharmacokineticmodel. The average drug concentration at steadystate is expected to be reduced with increasing body weight.

AB - Objective: The purpose of this analysis was to develop apopulation pharmacokinetic model for a novel recombinanthuman follicle-stimulating hormone (FSH) (FE 999049)expressed from a human cell line of foetal retinal origin(PER.C6) developed for controlled ovarian stimulation priorto assisted reproductive technologies.Methods: Serum FSH levels were measured following asingle subcutaneous FE 999049 injection of 37.5, 75, 150,225 or 450 IU in 27 pituitary-suppressed healthy femalesubjects participating in this first-in-human single ascendingdose trial. Data was analysed by nonlinear mixedeffects population pharmacokinetic modelling in NONMEM7.2.0.Results: A one-compartment model with first-orderabsorption and elimination rates was found to best describethe data. A transit model was introduced to describe a delayin the absorption process. The apparent clearance (CL/F)and apparent volume of distribution (V/F) estimates werefound to increase with body weight. Body weight wasincluded as an allometrically scaled covariate with a powerexponent of 0.75 for CL/F and 1 for V/F.Conclusions: The single-dose pharmacokinetics of FE999049 were adequately described by a population pharmacokineticmodel. The average drug concentration at steadystate is expected to be reduced with increasing body weight.

U2 - 10.1007/s40268-016-0129-9

DO - 10.1007/s40268-016-0129-9

M3 - Journal article

VL - 16

SP - 173

EP - 180

JO - Drugs in R&D

JF - Drugs in R&D

SN - 1174-5886

IS - 2

ER -