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

Effects of Age and Sex on the Pharmacokinetics, Safety, and Tolerability of Oral Desvenlafaxine in Healthy Adults

Alice I Nichols, Lyette S Richards, Jessica A Behrle, Joel A Posener, Richard Fruncillo and Jeffrey Paul

Background: Desvenlafaxine (administered as desvenlafaxine succinate) is a serotonin-norepinephrine reuptake inhibitor approved for treatment of major depressive disorder. Because it is primarily eliminated unchanged by renal excretion, it is important to characterize the effect of patient factors, such as age and sex that may influence renal clearance. Methods: The pharmacokinetics, safety, and tolerability of a single oral dose of desvenlafaxine were assessed in healthy adults stratified by age (young, 18-45 years; elderly, 65-75; very old, >75) and sex in an open-label, inpatient trial. Results: Desvenlafaxine was generally well tolerated and was slowly absorbed in all age groups. Mean values for peak plasma concentration (C max ) for women exceeded those of men (P<0.001), and women had a shorter time to C max (P=0.011). Compared with young participants, mean total area under the plasma concentration-versus-time curve (AUC) and C max values were 55% and 32% higher in very old participants, respectively. These differences were largely driven by decline in renal function. Conclusion: There were small to moderate pharmacokinetic differences with oral desvenlafaxine across the age and sex cohorts; however, the magnitude of the differences do not warrant specific dose adjustments based solely on sex or age. The possibility of reduced renal clearance should be considered when determining the dose for patients aged >75 years.