Cacilda da Silva Souza

Venlafaxine, a serotonin‐norepinephrine reuptake inhibitor, is an antidepressant administered as a racemate of ( S )‐ and ( R )‐venlafaxine enantiomers, which differ in pharmacological activity. It is extensively metabolized, primarily via CYP2D6, to its major active metabolite, O ‐desmethylvenlafaxine. Variability in CYP2D6 activity, due to genetic polymorphisms or co‐administration with CYP2D6 inhibitors, can potentially alter exposure to both venlafaxine and O ‐desmethylvenlafaxine. This study aimed to quantify the impact of strong CYP2D6 inhibitor on the pharmacokinetics of venlafaxine and O ‐desmethylvenlafaxine and to evaluate whether dose adjustment is warranted when exposure to the active compounds is normalized by their relative pharmacodynamic potency. In a two‐phase crossover study, 24 subjects received a single oral dose of 150 mg racemic venlafaxine. Following a 2‐week washout period, a strong CYP2D6 inhibitor (paroxetine 20 mg) was administered daily for 10 days, with venlafaxine co‐administered on the final day. Enantiomer‐specific parent‐metabolite models were developed using nonlinear mixed‐effect modeling. A one‐compartment model with first‐order absorption, incorporating a first‐pass effect, and linear elimination was applied for both enantiomers. CYP2D6 inhibition reduced parent‐to‐metabolite conversion, with a 2.5‐fold greater effect on ( R )‐venlafaxine compared to ( S )‐venlafaxine. The co‐administration of CYP2D6 inhibitor reduced by ∼8% the potency‐adjusted exposure for norepinephrine and serotonin transporters. Although venlafaxine exposure increased under CYP2D6 inhibition, the magnitude of this effect was lower than that observed comparing CYP2D6 phenotypes. Therefore, dosing recommendations for venlafaxine in the presence of CYP2D6 inhibitors should be aligned with those for CYP2D6 intermediate metabolizers, for whom no dose adjustment is recommended.

BackgroundPsoriasis is a common cutaneous disease; however, information about psoriasis-related oral mucosal lesions is scarce in the literature.Case DescriptionWe report a case of a 73-year-old male patient with cutaneous and oral palatal alterations. An incisional biopsy of these lesions revealed psoriasis.ConclusionThe current case highlights the importance of a systematic examination of the oral cavity in psoriasis patients for the appropriate diagnosis and management on the control of these lesions.