Vorapaxar, an oral PAR-1 receptor antagonist, does not affect the pharmacokinetics of rosiglitazone.
Clin Pharmacol Drug Dev
; 4(1): 56-62, 2015 01.
Article
in En
| MEDLINE
| ID: mdl-27128003
ABSTRACT
PURPOSE:
To evaluate the potential effects of vorapaxar on the pharmacokinetics and safety of rosiglitazone.METHODS:
This was an open-label, two-period, two-treatment, fixed-sequence study in 18 healthy subjects. On Day 1, Period 1, subjects received a single dose of rosiglitazone 8 mg. In Period 2, subjects received vorapaxar 40 mg on Day 1, vorapaxar 7.5 mg once-daily on Days 2-7, and a single dose of rosiglitazone 8 mg on Day 7. Rosiglitazone and N-desmethylrosiglitazone pharmacokinetics were assessed alone (Period 1) and after coadministration with vorapaxar (Period 2). Vorapaxar and its M20 metabolite pharmacokinetics were assessed on Day 7, Period 2. Safety and tolerability were assessed throughout the study.RESULTS:
Coadministration of rosiglitazone with vorapaxar had no effect on rosiglitazone or N-desmethylrosiglitazone pharmacokinetics. The ratio of geometric means (GMR) and 90% confidence intervals (CI) of the coadministration versus monotherapy for Cmax (GMR 95; 90% CI 88, 103) and AUC0-24 h (GMR 103; 90% CI 98, 108) were within the 80-125% bioequivalence criteria. The metabolite-to-parent exposure ratio with and without vorapaxar was unaltered. Coadministration of vorapaxar with rosiglitazone was generally well tolerated.CONCLUSION:
Coadministration of vorapaxar with rosiglitazone or drugs metabolized via CYP2C8 is unlikely to cause a significant pharmacokinetic interaction.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyridines
/
Platelet Aggregation Inhibitors
/
Thiazolidinediones
/
Receptor, PAR-1
/
Cytochrome P-450 CYP2C8 Inhibitors
/
Hypoglycemic Agents
/
Lactones
Type of study:
Prognostic_studies
Limits:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
America do norte
Language:
En
Journal:
Clin Pharmacol Drug Dev
Year:
2015
Document type:
Article
Affiliation country:
United States