10 Sertraline is metabolized by CYP2D6, CYP2C19, and other polymorphic cytochrome P450 enzymes, with pharmacokinetic data suggesting that CYP2C19 is the major metabolic pathway (Supplemental Figure S1).
Is sertraline a CYP2D6 inhibitor?
Sertraline is a selective serotonin reuptake inhibitor (SSRI) effective as monotherapy in the treatment of major depression. Similar to other SSRIs, sertraline inhibits the activity of CYP2D6 in enzyme assays using human liver microsomes. However, sertraline is a less potent inhibitor than several other SSRI agents.
Which antidepressants are metabolized by CYP2D6?
CYP2D6 is involved in the metabolism of most antidepressants, and is primarily responsible for breakdown of amitriptyline, venlafaxine, fluoxetine and paroxetine among others. This enzyme also contributes to the metabolism of other antidepressants such as citalopram, duloxetine and mirtazapine.
What enzyme is sertraline metabolized by?
Sertraline is metabolized by multiple cytochrome P450 enzymes, monoamine oxidases, and glucuronyl transferases in human: an in vitro study. Drug Metab Dispos.
Does paroxetine inhibit CYP2D6?
Paroxetine, a selective serotonin reuptake inhibitor, is a potent inhibitor of cytochrome P450 2D6 (CYP2D6) activity, but the mechanism of inhibition is not established.
Where are SSRIs metabolized?
Psychotropic drugs, including many antidepressants, are usually lipophilic and are extensively metabolized in the liver through phase I oxidative reactions followed by phase II glucuronide conjugation.
Is citalopram metabolized by CYP2D6?
Citalopram is metabolized by three CYP enzymes. CYP2C19 and CYP3A4 play a primary role in citalopram metabolism, whereas CYP2D6 plays a secondary role.
Which SSRI has least drug interactions?
Citalopram and sertraline, which have relatively little effect on the P450 system and wash out of the body relatively quickly, are the least likely of the SSRIs to interact with a replacement drug.
What does CYP2D6 do in the body?
CYP2D6 is involved in the metabolism of many CNS drugs such as antidepressants, antipsychotics and opioids, as well as in the metabolism of endogenous neuroactive substrates (i.e. neuroactive monoamines, endocannabinoids and endomorphines).
Is sertraline metabolized in the liver?
Sertraline is metabolized at least in part by the liver, mainly via the cytochrome P450 system and PYP 2D6 and 2B6 which can cause drug-drug interactions.
Is sertraline metabolized by CYP?
The metabolism of sertraline is mainly catalyzed by CYP3A4 and CYP2B6, with some activity accounted for by CYP2C19 and CYP2D6. Since sertraline is extensively metabolized, excretion of unchanged drug in the urine is a minor route of elimination, with 12-14% of unchanged sertraline excreted in the feces.
How does zoloft metabolize?
ZOLOFT is extensively metabolized by the liver. In patients with chronic mild liver impairment, sertraline clearance was reduced, resulting in increased AUC, Cmax and elimination half-life.
How is paroxetine metabolized?
Paroxetine is extensively metabolized and the metabolites are considered to be inactive. Nonlinearity in pharmacokinetics is observed with increasing doses. Paroxetine metabolism is mediated in part by CYP2D6, and the metabolites are primarily excreted in the urine and to some extent in the feces.
Does amitriptyline inhibit CYP2D6?
Because standard doses of amitriptyline may lead to an increased risk of adverse events in individuals who are CYP2D6 poor metabolizers, CPIC recommends avoiding the use of amitriptyline or other tricyclic antidepressants, and to consider using an alternative drug that is not metabolized by CYP2D6.