生物学的同等性とバイオアベイラビリティのジャーナル

概要

Bioequivalence and Pharmacokinetic Evaluation of Two Formulations of Armodafinil 250 mg Tablets in Healthy Indian Adult Male Subjects

Menon S, Kandari K, Mhatre M and Nair S

Armodafinil the R-enantiomer of modafinil is involved in managing sleep disorder consisting of excessive sleepiness associated with obstructive sleep apnea, narcolepsy and shift work disorder. The aim of the study was to establish bioequivalence and tolerability between two formulations of armodafinil. This was an oral comparative bioequivalence study in healthy Indian subjects. The study design was a crossover, randomized, open label single- dose, two-treatment, two-period, two-sequence type. Under fasting condition all the subjects (26 + 4 stand-by) received test and reference formulation in a staggered manner by a randomization code list in both the period with a washout period of seven days between the treatment periods. Twenty blood samples were drawn from each subject over 96 hours in each period. Liquid- liquid extraction method was validated using high performance liquid chromatography. The pharmacokinetic parameter Cmax (ng/ml), Tmax (hr), AUC(0-t) (ng/ml*hr), and AUC(0-∞) (ng/ml*hr), T½ (hr) and Kel (hr-1) were determined for armodafinil in reference and test formulations. ANOVA showed no significant variation in these parameters. Relative bioavailability of 97.78% was calculated for armodafinil. The 90% confidence interval of log transformed data comparing test formulation versus reference formulations for Cmax, AUC(0-t) and AUC(0-∞) are within the acceptance range of bioequivalence (80% to 125%). Based on the pharmacokinetics parameters of armodafinil (test and reference), it is concluded that single dose of single dose of armodafinil tablet containing 250 mg armodafinil manufactured by Emcure Pharmaceuticals, India., is bioequivalent to single dose of Nuvigil tablet containing 250 mg armodafinil manufactured by Cephalon, Inc., USA.