Bioequivalence study of 75 mg venlafaxine hydrochloride extended release capsules in healthy Thai volunteers.

ABSTRACT

Objective: The purpose of this study is to determine the bioequivalence of a 75 mg dose of venlafaxine hydrochloride extended release capsule formulations between the test product (Valosine® S.R., Standard Chem. & Pharm. Co., Ltd., Taiwan) and the reference product (Efexor®-XR, Wyeth-Ayerst Ireland Co., Ltd). Methods: An open-labeled, multiple-dose with food, 2-treatment, 2-period, 2-sequence, randomized crossover study was conducted in 24 healthy Thai volunteers. Each volunteer received a 75 mg capsule of the reference or test drugs for 6 consecutive days. On the 6th day of dosing, blood samples were collected before dosing at various time points up to 24 hours after dosing and on the other days (the 1st, 4th and 5th day of dosing) pre-dose blood samples were also collected for steady state confirmation. Analysis of venlafaxine concentrations was performed using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. The pharmacokinetic parameters including Cssmax, AUC0-24(ss), Tssmax and t1/2 were analyzed using the non-compartmental model. Drug safety and tolerability were assessed. Results: Twenty-three volunteers completed both treatment periods. The geometric mean ratios (Test/Reference) between the two products of extended-release venlafaxine capsule were 88.80% (81.46%-96.80%) for Cssmax ratios and 101.10% (95.02%-107.56%) for AUC0-24(ss) ratios. There was no significant difference of the Tssmax parameter between the two formulations (p >0.05). No serious adverse events related to the study drugs were found. Conclusion: The two products of venlafaxine hydrochloride extended release capsules are bioequivalent. Both products are well tolerated.