Population pharmacokinetic/pharmacodynamic assessment of pharmacological effect of a selective estrogen receptor β agonist on total testosterone in healthy men.
Journal:
Clinical pharmacology in drug development
PMID:
27136911
Abstract
BACKGROUND: LY500307 is a highly selective estrogen receptor β (ERβ) agonist, which loses its selectivity at high dose and leads to undesirable suppression of total testosterone (TT) concentration. The objective of the present analysis was to define the LY500307 dose with minimal effect on TT METHODS: LY500307 and TT concentrations were obtained from a single ascending-dose study in a total of 30 healthy male subjects. LY500307 (in the range of 0.5 to 500 mg) or placebo was administered orally as a single dose on 2 occasions with a 3-week washout period. A population pharmacokinetics/pharmacodynamics (PK/PD) model that integrated Fourier series in an indirect response model was developed to describe the circadian rhythm of TT and the exposure-response relationship of LY500307 on TT.
Authors
Keywords
Administration, Oral
Adult
Benzopyrans
Biomarkers
Circadian Rhythm
Cross-Over Studies
Drug Administration Schedule
Estrogen Receptor beta
Fourier Analysis
Healthy Volunteers
Humans
London
Male
Middle Aged
Models, Biological
Nonlinear Dynamics
Selective Estrogen Receptor Modulators
Single-Blind Method
Testosterone
Young Adult