जैवसमतुल्यता एवं जैवउपलब्धता जर्नल

अमूर्त

Pharmacokinetics and Tolerability of Single and Multiple Doses of Desvenlafaxine in Healthy Korean Subjects

Liang Y, Qiu R, Kim S, Jang IJ, Lee WS, Plotka A and Nichols A

Background: Racial and ethnic variations in CYP enzyme polymorphisms have been associated with population differences in drug metabolism. This study evaluated the pharmacokinetics of single- and multiple-dose desvenlafaxine in healthy Korean subjects.

Methods: This randomized, double-blind, placebo-controlled, study enrolled 38 healthy Korean adults (aged 18 to 55 years). Subjects received single oral doses of placebo or desvenlafaxine (administered as desvenlafaxine succinate) 50, 100, or 200 mg on day 1, followed by 5 days of once daily dosing on days 4 to 8. Blood samples were collected pre-dose and over 72 h post-dose on days 1 and 8. Plasma desvenlafaxine concentrations were measured using a validated high-performance liquid chromatography tandem mass spectrometry and pharmacokinetic parameters were calculated using non-compartmental method. Tolerability was assessed through adverse event reporting.

Results: For both single-and multiple-dose desvenlafaxine, peak plasma concentration and area under the concentration-time curve increased approximately linearly with dose. For the 4-fold increase in dose from 50 mg to 200 mg desvenlafaxine, area under the concentration-time curve from time 0 extrapolated to infinite time for singledose and area under the concentration-time curve from time 0-24 h for multiple-dose administration increased 4.3- and 4.1-fold, respectively; peak plasma concentration values increased 4.5- and 4.3-fold, respectively. Mean apparent half-life ranged from 10.75-13.49 h across all doses following single and multiple dose administration. Accumulation ratios for area under the concentration-time curve ranged from 1.478 to 1.669 (peak plasma concentration, 1.488- 1.578). No serious or severe adverse events were reported.

Conclusion: The pharmacokinetics of multiple-dose desvenlafaxine 50-200 mg was linear and was able to be predicted from single-dose pharmacokinetics in Korean subjects. Pharmacokinetic parameters were similar to values previously observed in other racial/ethnic populations. There were no new safety findings for desvenlafaxine.