Effects of age and gender on venlafaxine and O-desmethylvenlafaxine pharmacokinetics.
This single- and multiple-dose, nonrandomized, inpatient study was conducted to determine the effects of age and gender on the pharmacokinetic profiles of the antidepressant venlafaxine and its equally active metabolite, O-desmethylvenlafaxine. The subjects were 18 elderly (age 60-80 yrs) and 18 young (age 21-44 yrs) subjects, 9 men and 9 women per age group. They received a single 50-mg venlafaxine dose followed by 50-mg doses every 8 hours for 5 days. No significant differences in venlafaxine single-dose pharmacokinetics were seen between age groups, but the steady-state half-life increased 24% in the elderly. For O-desmethylvenlafaxine, single doses had a significantly lower apparent clearance in the elderly (0.29 vs 0.38 L/hr/kg), longer half-life (13.2 vs 10.3 hrs), and 14% greater steady-state half-life. For the composite (venlafaxine+O-desmethylvenlafaxine), there was a nonsignificant 16% increase in elderly steady-state area under the curve (AUC* = AUC+activity factor AUCm), and AUC* was linear between doses and age groups. We conclude that venlafaxine dosage adjustments for age or gender are not necessary based on pharmacokinetics.
Division of Clinical Research and Development, Wyeth-Ayerst Research, Philadelphia, Pennsylvania 19101-1245, USA.
K J
KJ
Klamerus
V D
VD
Parker
R L
RL
Rudolph
A T
AT
Derivan
S T
ST
Chiang
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D018687:Antidepressive Agents, Second-Generation / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D003511:Cyclohexanols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000069468:Desvenlafaxine Succinate; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics*; D012737:Sex Factors; D000069470:Venlafaxine Hydrochloride
D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; D000069468:Desvenlafaxine Succinate; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride