Abstract

BIOEQUIVALENCE STUDY OF DOFETILIDE IN HEALTHY HUMAN VOLUNTEERS UNDER FASTING AND FED CONDITIONS

R Arunkumar*, A Ruckmani, Lakshmipathy Prabhu R, Pradeep G Nayar, MChokkalingam, D Rajasekaran, O Arjun Arumugam

Abstract

Dofetilide is an antiarrhythmic agent belonging to class III. It is indicated for the conversion and maintenance of sinus rhythm in atrial fibrillation and atrial flutter. The objective of this study is to investigate the bioequivalence of generic dofetilide 0.5 mg in comparison with Tikosyn ® (dofetilide) 0.5 mg under fasting and fed conditions in healthy human volunteers. The study was designed as a “two period, two treatment, two way, cross over, open label” study. 12 healthy, adult, male subjects were enrolled after obtaining written informed consent. Six of them received the medications under fasting conditions and the remaining six under fed conditions, both generic and innovator drugs with the wash out period of 5 days in between. Blood samples were collected for dofetilide estimation in K3EDTA blood collection tubes. QTc interval was recorded at scheduled time points to assess the effect of the drug on ECG. There was no adverse effect observed during the study. The generic and innovator products were well tolerated. Both the formulations produced an increase in the QTc interval, which returned pre-dose level within 8 to 12 hours. The drug concentration was measured using LCMSMS with the validated bioanalytical method. Pharmacokinetic and statistical analysis were done using WinNonlin® and SAS®. The results indicate that the generic dofetilide produced pharmacokinetic parameters cmax, AUC0-t and AUC0-inf that met bioequivalence limits of 80-125 under fasting conditions but failed to meet the BE limits under fed conditions for cmax whereas it met the limits for AUC0-t and AUC0-inf.

Keywords: Dofetilide, bioequivalence, generic drug, pharmacokinetics