Duloxetine (LY-248686) is a potent inhibitor of serotonin (5-hydroxytryptamine, 5-HT) and noradrenaline (NE) uptake in vitro and in vivo and is 3- to 5-times more effective at inhibiting 5-HT uptake.
Duloxetine is a potent inhibitor of serotonin (5-HT) and norepinephrine reuptake. Compared with its effects on 5-HT and norepinephrine reuptake, duloxetine weakly inhibits dopamine reuptake and has low binding affinity for other neurotransmitter receptors, including adrenergic, muscarinic (nonselective) and histamine H1 receptors; dopamine D2 receptors; 5-HT1A, 5-HT1D and 5-HT2C receptors; and opioid receptors. In vitro studies showed that more than 90% of duloxetine is protein bound in human plasma. The binding occurs primarily to albumin and a1-acid glycoprotein[1].
Duloxetine achieves a maximum plasma concentration (Cmax) of approximately 47 ng/mL (40mg twice-daily dosing) to 110 ng/mL (80 mg twice-daily dosing) approximately 6 hours after dosing. The elimination half-life of duloxetine is approximately 10–12 hours and the volume of distribution is approximately 1640 L. The absolute oral bioavailability averaged 50%, ranging from 30% to 80%, after a 60 mg single dose in one study and averaged 43%, ranging from 19% to 71%, in another study. Food and time of day impact duloxetine absorption, with food and bedtime administration delaying tmax by 4 hours[1].
[1] Knadler MP, et al. Clin Pharmacokinet. 2011, 50(5):281-94.