Population pharmacokinetics of fingolimod phosphate in healthy participants.
J Clin Pharmacol
; 52(7): 1054-68, 2012 Jul.
Article
in En
| MEDLINE
| ID: mdl-22110161
ABSTRACT
Fingolimod (FTY720) is a sphingosine 1-phosphate receptor (S1PR) modulator currently being evaluated for the treatment of multiple sclerosis. Fingolimod undergoes phosphorylation in vivo to yield fingolimod phosphate (fingolimod-P), which modulates S1PRs expressed on lymphocytes and cells in the central nervous system. The authors developed a population model, using pooled data from 7 phase 1 studies, to enable characterization of fingolimod-P pharmacokinetics following oral administration of fingolimod and to evaluate the impact of key demographic variables on exposure. The fingolimod-P concentration-time course after either single or multiple doses of fingolimod was described by a 2-compartment model with first-order apparent formation and elimination, lag time in the apparent formation, and dose-dependent relative bioavailability and apparent central volume of distribution. Body weight and ethnicity were identified as demographic covariates correlated with the disposition of fingolimod-P. Model predictions indicated no need for dose adjustment of fingolimod based on body weight; the effect of ethnicity on the disposition of fingolimod requires further investigation. The accurate prediction of the pharmacokinetic profile of fingolimod-P determined empirically in 2 large phase 3 trials provides external validation of the model.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Propylene Glycols
/
Sphingosine
/
Immunosuppressive Agents
/
Models, Biological
Type of study:
Prognostic_studies
/
Systematic_reviews
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
J Clin Pharmacol
Year:
2012
Document type:
Article
Affiliation country:
United States