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Effect of food on the pharmacokinetics and pharmacodynamics of R1663, an oral factor Xa inhibitor, in healthy male volunteers.
MedLine Citation:
PMID:  22735461     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Aims: To explore the effect of food intake on the relative bioavailability of R1663 and on its pharmacodynamic effects (prothrombin time (PT) and activated partial thromboplastin time (aPTT)) after a single oral dose of 200 mg. Methods: This was a prospective, open-label, randomized, two-way crossover study. Eight healthy male volunteers received R1663 on two occasions, after a high fat/high calorie breakfast and after an overnight fast of 10 h, with a 7-day washout between doses. Blood was sampled up to 48 h for the pharmacokinetic and pharmacodynamic evaluation of R1663. Pharmacokinetic parameters (area under the plasma concentration-time curve from Time 0 extrapolated to infinity (AUC0-∞) and maximal concentration (Cmax)) as well as pharmacodynamic parameters (area under the effect curve over 48 h (AUE0-48) and maximal effect (Emax)) were determined on both occasions. Geometric mean ratios fed/ fasted (GMR) and 90% confidence intervals (CI) were calculated for AUC0-∞ and Cmax of R1663 and AUE0-48 and Emax of PT and aPTT. Results: Following food intake, Cmax was reduced by 10% with CI extended outside the bioequivalence range (GMR, 0.90; CI 0.72 - 1.13). R1663 tmax was delayed in the fed state (4 h) as compared to the fasted state (1 h). There was no significant food effect on R1663 AUC0-∞ (GMR, 1.09; CI 0.97 - 1.24). Although the Emax of PT showed statistically significant reduction with food, the 90% CIs for Emax and AUE0-48 of PT and aPTT were all contained within the bioequivalence range (0.80 - 1.25). Conclusions: These findings will allow the administration of R1663 without regard to food in the upcoming trials.
Authors:
Christophe Schmitt; Anne Charoin-Pannier; Christine McIntyre; Hagen Zandt; Cornelia Ciorciaro; Lydia Zweigler; Katie Winters; Tom Pepper
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-26
Journal Detail:
Title:  International journal of clinical pharmacology and therapeutics     Volume:  -     ISSN:  0946-1965     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9423309     Medline TA:  Int J Clin Pharmacol Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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