Population Pharmacokinetic Modelling of FE 999049, a Recombinant Human Follicle-Stimulating Hormone, in Healthy Women After Single Ascending Doses
(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
- Rose, Trine Høyer ; Röshammar, Daniel ; Erichsen, Lars ; Grundemar, Lars LU and Ottesen, Johnny T
- publishing date
- 2016-06
- type
- 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
- external identifiers
-
- scopus:84961784569
- pmid:27003895
- 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
- 2024-01-04 22:38:42
@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}},
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}},
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}},
doi = {{10.1007/s40268-016-0129-9}},
volume = {{16}},
year = {{2016}},
}