title: Establishing bioequivalence of racemic venlafaxine formulations using stereoselective assay method: Is it necessary?
abstract: A bioequivalence study for venlafaxine generic formulation was conducted as an open label, balanced, randomized, two-way crossover, single-dose study. In this study, a comparison of various pharmacokinetic parameters of venlafaxine hydrochloride 150 mg modified release capsules of Ranbaxy and EFEXOR®-XR 150 mg capsules of Wyeth, in healthy, adult, male, human subjects under fasting condition was performed to conclude bioequivalence. Venlafaxine and its major active metabolite O-desmethylvenlafaxine (ODV) are racemates. The "(S)-(+)" and "(R)-(-)" enantiomers of venlafaxine and ODV are established as being active. Hence, subject samples were analyzed using nonstereoselective and stereoselective assay methods. Both (S)-(+) and (R)-(-) enantiomers of venlafaxine and ODV showed similar absorption and disposition. The 90% confidence intervals for venlafaxine, (R)-(-)-venlafaxine as well as (S)-(+)-venlafaxine were within acceptance range concluding bioequivalence. The results obtained by stereoselective assay were comparable to the nonstereoselective analysis, as sum of concentrations of (S)-(+)- and (R)-(-)-enantiomers of venlafaxine and ODV. The mean (S)-(+)/(R)-(-) ratios of the enantiomers of venlafaxine and ODV at various time points were consistent in the study subjects. Therefore, the estimation of venlafaxine and ODV using nonstereoselective assay method is effective in distinguishing formulation differences (if any) in bioequivalence studies in a cost-effective manner.
authors.affiliation: Department of Clinical Pharmacology and Pharmacokinetics, Ranbaxy Research Laboratories, Gurgaon, Haryana, India. Kirti.kandhwal@ranbaxy.com, kirti.kandhwal@gmail.com.
authors.forename: Kirti
authors.initials: K
authors.lastname: Kandhwal
authors.forename: Surajit
authors.initials: S
authors.lastname: Dey
authors.forename: Shabana
authors.initials: S
authors.lastname: Nazarudheen
authors.forename: Simrit
authors.initials: S
authors.lastname: Reyar
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Mishra
authors.forename: Nageshwar R
authors.initials: NR
authors.lastname: Thudi
authors.forename: Arshad H
authors.initials: AH
authors.lastname: Khuroo
authors.forename: Tausif
authors.initials: T
authors.lastname: Monif
mesh_terms: D000328:Adult; D002626:Chemistry, Pharmaceutical; D003511:Cyclohexanols / Q000737:chemistry* / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D013237:Stereoisomerism; D013810:Therapeutic Equivalency; D000069470:Venlafaxine Hydrochloride; D055815:Young Adult
chemical_list: D003511:Cyclohexanols; D000069470:Venlafaxine Hydrochloride