ABSTRACT
Atomoxetine is a drug widely used for the treatment of the attention deficit hyperactivity disorder (ADHD) with reduced risk of adverse motor reactions and chemical dependence. However, the pharmacokinetics characteristics as well as the toxicological risk of atomoxetine deserves further investigation to comprehensively analyze the therapeutic and safety aspects of this drug. This study aimed to predict the physicochemical profile and medicinal chemistry characteristics of atomoxetine, alongside its pharmacokinetic properties-namely absorption, distribution, metabolism, and excretion-as well as its toxicology (ADMET) potential through the utilization of web-based in silico tools. This research emphasizes predicted physicochemical, medicinal chemistry, and absorption parameters of atomoxetine that could influence the efficacy and safety of this drug for ADHD treatment. Additionally, atomoxetine also presents noteworthy predicted risks of hepatotoxicity, cardiotoxicity, neurotoxicity, nephrotoxicity, respiratory system toxicity, skin toxicity, and carcinogenicity. These findings underscore the necessity for further assessments of atomoxetine's safety profile, particularly considering different patient populations and durations of drug treatment. The data reported here from in silico predictions suggest that closer monitoring is warranted when atomoxetine is administered to patients with ADHD. Moreover, controlled studies detailing reliable protocols for personalized dosing, considering the multifactorial variability in metabolism efficiency and toxicological potential, would enable a more comprehensive assessment of atomoxetine's safety profile.
Subject(s)
COVID-19 , Homeopathy , Humans , Double-Blind Method , Pharmaceutical Preparations , Treatment OutcomeABSTRACT
Congenital toxoplasmosis is a parasitic disease caused by Toxoplasma gondii, an obligate intracellular parasite which can cause fetal death/abortion and can induce damage in the brain and eyes of the infected babies. The environmental and genetic factors associated with T. gondii and the maternal immune response, drive part of the pathogenesis of congenital toxoplasmosis. Thus, in this study, we aimed to investigate the allelic and genotypic frequencies of specific single nucleotide polymorphisms (SNPs) in the IL17A and IL17RA genes, as well as the production of IL-17A, IL-33, and CCL2 in pregnant women, from the State of Rio Grande do Norte, Brazil, further relating these along with the clinical parameters, to the toxoplasmosis infection. Through PCR-RFLP techniques, two SNPs implicated in Th17 immune response, IL17A rs2275913 (G> A) and IL17RA rs4819554 (A> G) modulation were evaluated in pregnant women, either infected or not infected by T. gondii. These women were also evaluated in terms of plasma release of CCL2, IL-33, and IL-17A which relate to hypertension, number of abortions, and ethnic pattern. The results showed that the G-allele of the SNP rs2275913 (IL17A) appeared to be protective in this population, while the rs4819554 (IL17RA) SNP G allele was associated with greater susceptibility to T. gondii infection [ρ value = 0.025; OR = 2.815 (1.118-7.089); CI = 95%]. None of the cytokines had any influence on the analyzed parameters (abortion and hypertension). In conclusion, our data suggest an immunogenic evidence of susceptibility to T. gondii infection driven by the rs4819554 (IL17RA) SNP G allele in Brazilian pregnant women. Further studies are needed to reinforce this trial marker in populations from distinct geographical areas as well as to confirm the protective pattern related to the G-allele of the SNP rs2275913 (IL17A) in pregnant women.