Enzymes, receptors, and other binding molecules in biological processes can recognize enantiomers as different molecular entities, due to their different dissociation constants, leading to diverse responses in biological processes. Enantioselectivity can be observed in drugs pharmacodynamics and in pharmacokinetic (absorption, distribution, metabolism, and excretion), especially in metabolic profile and in toxicity mechanisms. The stereoisomers of a drug can undergo to different metabolic pathways due to different enzyme systems, resulting in different types and/or number of metabolites. The configuration of enantiomers can cause unexpected effects, related to changes as unidirectional or bidirectional inversion that can occur during pharmacokinetic processes. The choice of models for pharmacokinetic studies as well as the subsequent data interpretation must also be aware of genetic factors (such as polymorphic metabolic enzymes), sex, patient age, hepatic diseases, and drug interactions. Therefore, the pharmacokinetics and toxicity of a racemate or an enantiomerically pure drug are not equal and need to be studied. Enantioselective analytical methods are crucial to monitor pharmacokinetic events and for acquisition of accurate data to better understand the role of the stereochemistry in pharmacokinetics and toxicity. The complexity of merging the best enantioseparation conditions with the selected sample matrix and the intended goal of the analysis is a challenge task. The data gathered in this review intend to reinforce the importance of the enantioselectivity in pharmacokinetic processes and reunite innovative enantioselective analytical methods applied in pharmacokinetic studies. An assorted variety of methods are herein briefly discussed.
Fluvoxamine is a selective-serotonin reuptake inhibitor (SSRI), well-tolerated and widely available, usually used in the management of mental-health conditions. Fluvoxamine is also a sigma-1 agonist with high affinity to this receptor and this pharmacodynamical effect has been being portrayed as the main explanation in emerging evidence about the potential of using fluvoxamine in COVID-19 patients. This systematic review was conducted according to the PRISMA guidelines. The search was run in MEDLINE, Web of Science, and CENTRAL from the Cochrane databases. The study protocol was registered in PROSPERO (CRD42022302025). Our aim was to assess the present evidence for therapeutic role of fluvoxamine in COVID-19 patients, the review included studies which evaluate the effect of fluvoxamine in COVID-19 patients. The main outcomes evaluated in the review were: mortality, need for hospitalization (outpatients) and clinical deterioration. The quality control of the selected articles was made using Cochrane’s Risk of Bias tool for the randomized controlled trials (RCTs) and the ROBINS-I criteria for non-randomized studies. A total of 4 studies were included in the final qualitative analysis of the review, 2 of which were RCTs, and the others were open-label prospective cohorts. 3 studies assessed outpatient population and 1 evaluated ICU population. Overall, the 4 studies included a total of 1864 participants. In conclusion, 3 studies with outpatients showed that fluvoxamine treatment can prevent clinical deterioration, hospitalisation, or proxy-hospitalisation. The only study with patients hospitalized in the ICU also demonstrated a therapeutic benefit reducing overall mortality.
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