Clinically relevant pharmacokinetic drug interactions with second-generation antidepressants: An update

Structural Characterization of Human Cytochrome P450 2C19

“…Allelic variation in human populations leads to significant differences among individuals in P450 2C19 expression and metabolic capacity that underlie poor, extensive and ultra-fast phenotypes for drug clearance. These phenotypes are evident for the clearance of S-mephenytoin (3) as well as for a number of antidepressants and serotonin reuptake inhibitors (1,4,5). Inter-individual differences in P450 2C19 metabolic capacity can also alter the clearance of omeprazole and structurally related inhibitors of gastric acid secretion leading to differences in clinical outcomes and dosing requirements (6).…”

Iatrogenic Menopause After Treatment for Cervical Cancer

“…Serotonin-norepinephrine and Selective serotonin reuptake inhibitors (SNRIs/SSRIs), The SNRI most commonly used is venlafaxine, especially in breast cancer patients [87], since it has a weak/negligible effect on cytochrome P450 unlike other SNRIs, for example fluoxetine and paroxetine, which are strong inhibitors of this enzyme system [88] and therefore reduce the efficacy of concomitant medication, in particular tamoxifen and other chemotherapeutic agents [89]. Venlafaxine can significantly reduce hot flushes and sweats and is used in doses up to 75 mg daily.…”

Pharmacogenetics of antidepressant drugs: An update

“…The metabolic activity of CYPs is genetically determined and mutations or polymorphisms in genes coding for CYP isoforms can result in enzyme variants with higher, lower or no activity. As shown in Table 1, the isoenzymes CYP1A2, CYP2C9/19, CYP2D6, and CYP3A4 are the major enzymes that catalyze antidepressant metabolic reactions [21]. In particular, most ADs are metabolized by polymorphic CYP2D6 and CYP2C19, and the differences in pharmacokinetic parameters like clearance or half-lives between the specific genotypes are extensively large [22,23].…”