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

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.