Rosa Direito
@imed.ulisboa.pt
Laboratory of Systems Integration Pharmacology, Clinical & Regulatory Science
Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa
Rosa Direito earned her PhD in Pharmacy (Food Science), having been awarded a fellowship by the Dean of the University of Lisbon. She has a background in experimental models of disease, mainly on animal models of acute and chronic inflammation (ulcerative colitis, rheumatoid arthritis) and in vitro model of colon cancer, and how certain fruits, vegetables and herbs can have an impact on inflammatory processes. Her research interests span the crossroads of the brain-gut axis and how diet and the microbiome can have an impact on health. Over the years she has also mentored and collaborated with students from different degrees, is certified in the handling of laboratory animals, and is an instructor of a postgraduate course on laboratory animal sciences. After finishing her PhD, she has sought to contribute to science internationally by becoming an active certified reviewer and has joined the board of reviewers and editorial board of several scientific journals.
EDUCATION
Post-doctoral Fellow (2021-2022), IHMT, Lisboa, Portugal
Post-doctoral Fellow (2020), Instituto Gulbenkian Ciência (IGC), Oeiras, Portugal
PhD (2019) in Pharmacy (Food Science), University of Lisbon, Lisbon, Portugal
MSc (2009) in Biochemistry, University of Coimbra, Coimbra, Portugal
BSc (2005) in Biochemistry, University of Coimbra, Coimbra, Portugal
RESEARCH INTERESTS
Her research interests span the crossroads of the brain-gut axis and how diet and the microbiome can have an impact on health.
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Luiz José Valotto Neto, Matheus Reverete de Araujo, Renato Cesar Moretti Junior, Nathalia Mendes Machado, Rakesh Kumar Joshi, Daiene dos Santos Buglio, Caroline Barbalho Lamas, Rosa Direito, Lucas Fornari Laurindo, Masaru Tanaka,et al.
MDPI AG
The aging of the global population has increased the prevalence of neurodegenerative conditions. Bacopa monnieri (BM), an herb with active compounds, such as bacosides A and B, betulinic acid, loliolide, asiatic acid, and quercetin, demonstrates the potential for brain health. Limited research has been conducted on the therapeutic applications of BM in neurodegenerative conditions. This systematic review aims to project BM’s beneficial role in brain disorders. BM has anti-apoptotic and antioxidant actions and can repair damaged neurons, stimulate kinase activity, restore synaptic function, improve nerve transmission, and increase neuroprotection. The included twenty-two clinical trials demonstrated that BM can reduce Nuclear Factor-κB phosphorylation, improve emotional function, cognitive functions, anhedonia, hyperactivity, sleep routine, depression, attention deficit, learning problems, memory retention, impulsivity, and psychiatric problems. Moreover, BM can reduce the levels of pro-inflammatory biomarkers and oxidative stress. Here, we highlight that BM provides notable therapeutic benefits and can serve as a complementary approach for the care of patients with neurodegenerative conditions associated with brain disorders. This review adds to the growing interest in natural products and their potential therapeutic applications by improving our understanding of the mechanisms underlying cognitive function and neurodegeneration and informing the development of new therapeutic strategies for neurodegenerative diseases.
Lucas Fornari Laurindo, Rosa Direito, Alda M. M. Bueno Otoboni, Ricardo Alvares Goulart, Karina Quesada, and Sandra Maria Barbalho
Informa UK Limited
Frantisek Drafi, Katarina Bauerova, Martin Chrastina, Mohsen Taghdisiesfejír, João Rocha, Rosa Direito, Maria Eduardo Figueira, Bruno Sepodes, and Silvester Ponist
MDPI AG
Rhodiola rosea L. extract (RSE) is mostly known for its adaptogen properties, but not for its antiarthritic activities, therefore monotherapy and combination with low-dose methotrexate (MTX) was studied. The collagen-induced arthritis (CIA) model was used to measure the functional score, and the change in hind paw volume (HPV). Both parameters had significant antiarthritic effects. Based on these preliminary results, an adjuvant arthritis (AA) model was further applied to assess another parameters. The experiment included these animal groups: healthy controls, untreated AA, AA administered with RSE (150 mg/kg b.w. daily, p.o.), AA administered by MTX (0.3 mg/kg b.w. twice a week, p.o.), and AA treated with the combination of RSE+MTX. The combination of RSE+MTX significantly reduced the HPV and increased the body weight. The combination significantly decreased HPV when compared to MTX monotherapy. The plasmatic levels of inflammatory markers (IL-6, IL-17A, MMP-9 and CRP) were significantly decreased by MTX+RSE treatment. The RSE monotherapy didn’t influence any of the inflammatory parameters studied. In CIA, the RSE monotherapy significantly decreased the arthritic parameters studied. In summary, the combination of RSE and sub-therapeutic MTX was significantly effective in AA by improving inflammatory and arthritic parameters.
Rosa Direito, Sandra Maria Barbalho, Maria Eduardo Figueira, Giulia Minniti, Gabriel Magno de Carvalho, Bárbara de Oliveira Zanuso, Ana Rita de Oliveira dos Santos, Natália de Góes Corrêa, Victória Dogani Rodrigues, Ricardo de Alvares Goulart,et al.
MDPI AG
Ongoing research explores the underlying causes of ulcerative colitis and Crohn’s disease. Many experts suggest that dysbiosis in the gut microbiota and genetic, immunological, and environmental factors play significant roles. The term “microbiota” pertains to the collective community of microorganisms, including bacteria, viruses, and fungi, that reside within the gastrointestinal tract, with a particular emphasis on the colon. When there is an imbalance or disruption in the composition of the gut microbiota, it is referred to as dysbiosis. Dysbiosis can trigger inflammation in the intestinal cells and disrupt the innate immune system, leading to oxidative stress, redox signaling, electrophilic stress, and inflammation. The Nod-like Receptor (NLR) Family Pyrin Domain Containing 3 (NLRP3) inflammasome, a key regulator found in immunological and epithelial cells, is crucial in inducing inflammatory diseases, promoting immune responses to the gut microbiota, and regulating the integrity of the intestinal epithelium. Its downstream effectors include caspase-1 and interleukin (IL)-1β. The present study investigated the therapeutic potential of 13 medicinal plants, such as Litsea cubeba, Artemisia anomala, Piper nigrum, Morus macroura, and Agrimonia pilosa, and 29 phytocompounds such as artemisitene, morroniside, protopine, ferulic acid, quercetin, picroside II, and hydroxytyrosol on in vitro and in vivo models of inflammatory bowel diseases (IBD), with a focus on their effects on the NLRP3 inflammasome. The observed effects of these treatments included reductions in IL-1β, tumor necrosis factor-alpha, IL-6, interferon-gamma, and caspase levels, and increased expression of antioxidant enzymes, IL-4, and IL-10, as well as regulation of gut microbiota. These effects could potentially provide substantial advantages in treating IBD with few or no adverse effects as caused by synthetic anti-inflammatory and immunomodulated drugs. However, additional research is necessary to validate these findings clinically and to develop effective treatments that can benefit individuals who suffer from these diseases.
Huseyin Ayvaz, Turgut Cabaroglu, Asiye Akyildiz, Cigdem Uysal Pala, Riza Temizkan, Erdal Ağçam, Zayde Ayvaz, Alessandra Durazzo, Massimo Lucarini, Rosa Direito,et al.
MDPI AG
In this work, various concepts and features of anthocyanins have been comprehensively reviewed, taking the benefits of the scientific publications released mainly within the last five years. Within the paper, common topics such as anthocyanin chemistry and occurrence, including the biosynthesis of anthocyanins emphasizing the anthocyanin formation pathway, anthocyanin chemistry, and factors influencing the anthocyanins’ stability, are covered in detail. By evaluating the recent in vitro and human experimental studies on the absorption and bioavailability of anthocyanins present in typical food and beverages, this review elucidates the significant variations in biokinetic parameters based on the model, anthocyanin source, and dose, allowing us to make basic assumptions about their bioavailability. Additionally, special attention is paid to other topics, such as the therapeutic effects of anthocyanins. Reviewing the recent in vitro, in vivo, and epidemiological studies on the therapeutic potential of anthocyanins against various diseases permits a demonstration of the promising efficacy of different anthocyanin sources at various levels, including the neuroprotective, cardioprotective, antidiabetic, antiobesity, and anticancer effects. Additionally, the studies on using plant-based anthocyanins as coloring food mediums are extensively investigated in this paper, revealing the successful use of anthocyanins in coloring various products, such as dietary and bakery products, mixes, juices, candies, beverages, ice cream, and jams. Lastly, the successful application of anthocyanins as prebiotic ingredients, the innovation potential of anthocyanins in industry, and sustainable sources of anthocyanins, including a quantitative research literature and database analysis, is performed.
Lucas Fornari Laurindo, Gabriel Magno de Carvalho, Bárbara de Oliveira Zanuso, Maria Eduardo Figueira, Rosa Direito, Ricardo de Alvares Goulart, Daiene Santos Buglio, and Sandra Maria Barbalho
MDPI AG
Curcumin (CUR) is a polyphenol extracted from the rhizome of Curcuma longa that possesses potent anti-inflammatory and antioxidant potential. Despite CUR’s numerous beneficial effects on human health, it has limitations, such as poor absorption. Nano-based drug delivery systems have recently been applied to improve CUR’s solubility and bioavailability and potentialize its health effects. This review investigated the effects of different CUR-based nanomedicines on inflammatory and immunomodulated diseases. PUBMED, EMBASE, COCHRANE, and GOOGLE SCHOLAR databases were searched, and the Scale for Assessment of Narrative Review Articles (SANRA) was used for quality assessment and PRISMA guidelines. Overall, 66 studies were included comprising atherosclerosis, rheumatoid arthritis (RA), Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), Huntington’s disease (HD), inflammatory bowel diseases (IBD), psoriasis, liver fibrosis, epilepsy, and COVID-19. The available scientific studies show that there are many known nanoformulations with curcumin. They can be found in nanosuspensions, nanoparticles, nanoemulsions, solid lipid particles, nanocapsules, nanospheres, and liposomes. These formulations can improve CUR bioavailability and can effectively be used as adjuvants in several inflammatory and immune-mediated diseases such as atheroma plaque formation, RA, dementia, AD, PD, MS, IBD, psoriasis, epilepsy, COVID-19, and can be used as potent anti-fibrotic adjuvants in fibrotic liver disease.
Daniela Franceschi Nishikito, Ana Claudia Abdalla Borges, LUCAS FORNARI LAURINDO, Alda M. M. Bueno Otoboni, R. Direito, R. Goulart, C. C. T. Nicolau, A. Fiorini, Renata Vargas Sinatora and S. Barbalho
Dragon fruit (Hylocereus genus) has the potential for the prevention of diseases associated with inflammatory and oxidative processes. We aimed to comprehensively review dragon fruit health effects, economic importance, and possible use in delivery systems. Pubmed, Embase, and Google Scholar were searched, and PRISMA (Preferred Reporting Items for a Systematic Review and Meta-Analysis) guidelines were followed. Studies have shown that pitaya can exert several benefits in conditions such as diabetes, dyslipidemia, metabolic syndrome, cardiovascular diseases, and cancer due to the presence of bioactive compounds that may include vitamins, potassium, betacyanin, p-coumaric acid, vanillic acid, and gallic acid. Moreover, pitaya has the potential to be used in food and nutraceutical products as functional ingredients, natural colorants, ecologically correct and active packaging, edible films, preparation of photoprotective products, and additives. Besides the importance of dragon fruit as a source of bioactive compounds, the bioavailability is low. The development of delivery systems such as gold nanoparticles with these compounds can be an alternative to reach target tissues.
Sandra Maria Barbalho, Rosa Direito, Lucas Fornari Laurindo, Ledyane Taynara Marton, Elen Landgraf Guiguer, Ricardo de Alvares Goulart, Ricardo José Tofano, Antonely C. A. Carvalho, Uri Adrian Prync Flato, Viviane Alessandra Capelluppi Tofano,et al.
MDPI AG
Neurodegenerative diseases, cardiovascular disease (CVD), hypertension, insulin resistance, cancer, and other degenerative processes commonly appear with aging. Ginkgo biloba (GB) is associated with several health benefits, including memory and cognitive improvement, in Alzheimer’s disease (AD), Parkinson’s disease (PD), and cancer. Its antiapoptotic, antioxidant, and anti-inflammatory actions have effects on cognition and other conditions associated with aging-related processes, such as insulin resistance, hypertension, and cardiovascular conditions. The aim of this study was to perform a narrative review of the effects of GB in some age-related conditions, such as neurodegenerative diseases, CVD, and cancer. PubMed, Cochrane, and Embase databases were searched, and the PRISMA guidelines were applied. Fourteen clinical trials were selected; the studies showed that GB can improve memory, cognition, memory scores, psychopathology, and the quality of life of patients. Moreover, it can improve cerebral blood flow supply, executive function, attention/concentration, non-verbal memory, and mood, and decrease stress, fasting serum glucose, glycated hemoglobin, insulin levels, body mass index, waist circumference, biomarkers of oxidative stress, the stability and progression of atherosclerotic plaques, and inflammation. Therefore, it is possible to conclude that the use of GB can provide benefits in the prevention and treatment of aging-related conditions.
Joana Mota, Rosa Direito, João Rocha, João Fernandes, Bruno Sepodes, Maria Eduardo Figueira, Anabela Raymundo, Ana Lima, and Ricardo Boavida Ferreira
MDPI AG
Matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) are regarded as important clinical targets due to their nodal-point role in inflammatory and oncological diseases. Here, we aimed at isolating and characterizing am MMP-2 and-9 inhibitor (MMPI) from Lupinus albus and at assessing its efficacy in vitro and in vivo. The protein was isolated using chromatographic and 2-D electrophoretic procedures and sequenced by using MALDI-TOF TOF and MS/MS analysis. In vitro MMP-2 and 9 inhibitions were determined on colon adenocarcinoma (HT29) cells, as well as by measuring the expression levels of genes related to these enzymes. Inhibitory activities were also confirmed in vivo using a model of experimental TNBS-induced colitis in mice, with oral administrations of 15 mg·kg−1. After chromatographic and electrophoretic isolation, the L. albus MMP-9 inhibitor was found to comprise a large fragment from δ-conglutin and, to a lower extent, small fragments of β-conglutin. In vitro studies showed that the MMPI successfully inhibited MMP-9 activity in a dose-dependent manner in colon cancer cells, with an IC50 of 10 µg·mL−1 without impairing gene expression nor cell growth. In vivo studies showed that the MMPI maintained its bioactivities when administered orally and significantly reduced colitis symptoms, along with a very significant inhibition of MMP-2 and -9 activities. Overall, results reveal a novel type of MMPI in lupine that is edible, proteinaceous in nature and soluble in water, and effective in vivo, suggesting a high potential application as a nutraceutical or a functional food in pathologies related to abnormally high MMP-9 activity in the digestive system.
Rosa Direito, João Rocha, Bruno Sepodes, and Maria Eduardo-Figueira
MDPI AG
Persimmon (Diospyros kaki L.) fruit’s phytochemical profile includes carotenoids, proanthocyanidins, and gallic acid among other phenolic compounds and vitamins. A huge antioxidant potential is present given this richness in antioxidant compounds. These bioactive compounds impact on health benefits. The intersection of nutrition and sustainability, the key idea behind the EAT-Lancet Commission, which could improve human health and decrease the global impact of food-related health conditions such as cancer, heart disease, diabetes, and obesity, bring the discussion regarding persimmon beyond the health effects from its consumption, but also on the valorization of a very perishable food that spoils quickly. A broad option of edible products with better storage stability or solutions that apply persimmon and its byproducts in the reinvention of old products or even creating new products, or with new and better packaging for the preservation of food products with postharvest technologies to preserve and extend the shelf-life of persimmon food products. Facing a global food crisis and the climate emergency, new and better day-to-day solutions are needed right now. Therefore, the use of persimmon waste has also been discussed as a good solution to produce biofuel, eco-friendly alternative reductants for fabric dyes, green plant growth regulator, biodegradable and edible films for vegetable packaging, antimicrobial activity against foodborne methicillin-resistant Staphylococcus aureus found in retail pork, anti-Helicobacter pylori agents from pedicel extracts, and persimmon pectin-based emulsifiers to prevent lipid peroxidation, among other solutions presented in the revised literature. It has become clear that the uses for persimmon go far beyond the kitchen table and the health impact consumption demonstrated over the years. The desired sustainable transition is already in progress, however, mechanistic studies and clinical trials are essential and scaling-up is fundamental to the future.
Rosa Direito, João Rocha, Bruno Sepodes, and Maria Eduardo-Figueira
MDPI AG
Non-communicable chronic diseases (NCDs) are nowadays the principal cause of death, especially in most industrialized nations. These illnesses have increased exponentially with the consumption of diets very high in fat and sugar, not to mention stress and physical inactivity among other factors. The potential impact of suboptimal diets on NCDs’ morbidity and mortality rates brings to the forefront the necessity for a new way of improving dietary habits. The literature provides extensive scientific work that presents evidence that phenolic compounds from diets have antioxidant, anti-inflammatory and antiproliferative activities that impact human health. Gut microbiota modulation by some phenolic compounds leads to favorable changes in abundance, diversity, and in the immune system. However, polyphenol’s limited bioavailability needs to be overcome, highlighting their application in new delivery systems and providing their health benefits in well-established ways such as health maintenance, treatment or adjuvant to conventional pharmacological treatments. In this context, novel dietary approaches, including new food supplements, have emerged to prevent diseases and preserve health.
João Rocha, Raquel Leandro, Rosa Direito, Margarida Gonçalves, Maria Paula Duarte, Adelaide Fernandes, Bruno Sepodes, and Maria-Eduardo Figueira
MDPI AG
Summer Savory (Satureja hortensis L.) is a plant traditionally used as a food spice in the Mediterranean region. Surprisingly, not much is known about the health beneficial effects of its phenolic-rich extracts. The majority of publications have always focused on the properties of their essential oil. One of the main phenolic compounds of Summer Savory is rosmarinic acid, which has demonstrated anti-inflammatory outcomes in several animal models of inflammatory-mediated diseases. Inflammatory Bowel Disease (IBD) is a chronic inflammatory disease, in addition to Ulcerative Colitis and Crohn’s Disease, frequently related with increased morbidity and even mortality due to the complications associated, including colorectal cancer. Our work has shown, to our knowledge, for the first time, that administration of a phenolic extract of Summer Savory in a mouse model of Ulcerative Colitis led to the reduction of several markers for intestinal injury, including reduction of inducible nitric oxide synthase (iNOS) and Cyclooxygenase-2 (COX-2 or prostaglandin-endoperoxide synthase) expression, two well-known mediators of tissue inflammation and progression to cancer and led also to a reduction of the mortality. Given the chemical constitution found in the extract and the preclinical evidence of a beneficial effect of polyphenols in inflammatory processes, an opportunity arises for pharmacological modulation of pathways relevant for IBD and progression to cancer with phenolic-rich extracts.
Rosa Direito, João Rocha, Ana-Teresa Serra, Adelaide Fernandes, Marisa Freitas, Eduarda Fernandes, Rui Pinto, Rosário Bronze, Bruno Sepodes, and Maria-Eduardo Figueira
Informa UK Limited
Abstract Persimmon (Diospyros kaki L.) fruits are used in traditional medicine largely due to their claimed beneficial effects on human health. The aim of this work was to evaluate the anti-inflammatory activity of a persimmon extract in rats with collagen-induced arthritis (CIA). CIA was induced in Wistar rats through an intradermal injection of an emulsion of bovine type II collagen (CII) in complete Freund’s adjuvant (FCA). Macroscopic evidence of CIA first appeared as periarticular erythema and edema in the hind paws. The incidence of CIA was 100% by day 27 in the CII-challenged rats, and the severity of CIA progressed for 35 days. Radiographs revealed focal resorption of bone, with osteophyte formation in the tibiotarsal joint and soft tissue swelling. The histopathologic features included erosion of the cartilage at the joint margins. The persimmon extract showed an anti-inflammatory effect given the significant reduction in both the edema volume and radiological alterations attributed to CIA in the bone. We demonstrate that the administration of persimmon extract attenuates the degree of chronic inflammation and tissue damage characteristic of CIA in rats, most probably by the potent antioxidant characteristics of the extract.
Carla Mendes, João Rocha, Rosa Direito, Adelaide Fernandes, Bruno Sepodes, Maria-Eduardo Figueira, and Maria H. Ribeiro
Elsevier BV
João Rocha, Rosa Direito, Ana Lima, Joana Mota, Margarida Gonçalves, Maria Paula Duarte, João Solas, Bruno Felício Peniche, Adelaide Fernandes, Rui Pinto,et al.
Elsevier BV
Rosa Direito, Catarina Reis, Luís Roque, Margarida Gonçalves, Ana Sanches-Silva, Maria Manuela Gaspar, Rui Pinto, João Rocha, Bruno Sepodes, Maria Rosário Bronze,et al.
MDPI AG
Persimmon (Diospyros kaki L.), a fruit rich in phenolic compounds (PCs), has been considered effective in mitigating oxidative damage induced by an excess of reactive oxygen species. Due to large molecular weight and intrinsic instability in some physiological fluids, PCs’ passage through biological membranes is very limited. Carriers like phytosomes are promising systems to optimize oral absorption of encapsulated extracts. This work prepared and fully characterized phytosomes containing bioactive phenolic extracts from persimmon in terms of size, surface charge, encapsulation efficiency and stability over six months. These phytosomes were orally dosed to Wistar rats during a 15-day period. Afterwards, haematological and biochemical analyses were performed. Monodisperse phytosomes were successfully prepared, with size less than 300nm (PI < 0.3) and high encapsulation efficiency (97.4%) of PCs. In contrast to free extract, extract-loaded phytosomes had higher antioxidant activity after 6 months storage. Oral administration of extract-loaded phytosomes and free extract did not lead to lipidic profile changes and were within referenced normal ranges, as well as glycaemia levels and urine parameters. The results highlighted the potential of persimmon PCs as food supplements or pharmacological tools, suggesting a promising and safe phytosomal formulation containing bioactive agents of persimmon that could lead to health benefits.
Ana Henriques Mota, Rosa Direito, Marta P. Carrasco, Patrícia Rijo, Lia Ascensão, Ana Silveira Viana, João Rocha, Maria Eduardo-Figueira, Maria João Rodrigues, Luísa Custódio,et al.
Elsevier BV
Susana A. Vieira da Silva, Ana Clemente, João Rocha, Rosa Direito, Helena Cabral Marques, Bruno Sepodes, Maria-Eduardo Figueira, and Maria H. Ribeiro
Elsevier BV
Rosa Direito, Ana Lima, João Rocha, Ricardo Boavida Ferreira, Joana Mota, Patrícia Rebelo, Adelaide Fernandes, Rui Pinto, Paula Alves, Rosário Bronze,et al.
Elsevier BV
Maria-Eduardo Figueira, Mónica Oliveira, Rosa Direito, João Rocha, Paula Alves, Ana-Teresa Serra, Catarina Duarte, Rosário Bronze, Adelaide Fernandes, Dora Brites,et al.
Elsevier BV
S. Silva, B. Sepodes, J. Rocha, R. Direito, A. Fernandes, D. Brites, M. Freitas, E. Fernandes, M.R. Bronze, and M.E. Figueira
Elsevier BV
M. E. Figueira, M. B. Câmara, R. Direito, J. Rocha, A. T. Serra, C. M. M. Duarte, A. Fernandes, M. Freitas, E. Fernandes, M. C. Marques,et al.
Royal Society of Chemistry (RSC)
A red raspberry extract reduces inflammation and the development of clinical signs of arthritis in Wistar rats.
Gilberto Alves, Ana Fortuna, Joana Sousa, Rosa Direito, Anabela Almeida, Marília Rocha, Amílcar Falcão, and Patrício Soares-da-Silva
Ovid Technologies (Wolters Kluwer Health)
As add-on therapy, phase III clinical trials of eslicarbazepine acetate (ESL) conducted in patients with refractory partial-onset seizures have shown good efficacy, safety, and tolerability, even in patients taking carbamazepine (CBZ) at baseline (approximately 60% of the enrolled patients). Thus, considering the pharmacological disadvantages of CBZ and the similar efficacy spectrum of CBZ and ESL, switching to ESL may be successful in many patients. As ESL is a prodrug almost instantaneously converted to S-licarbazepine (S-Lic; approximately 95%), an interest in therapeutic drug monitoring (TDM) of S-Lic is likely to develop in the future. This study investigated the plasma concentrations of S-Lic and R-licarbazepine (R-Lic) enantiomers in patients under CBZ long-term treatment to assess the potential interference of CBZ or its metabolites in the enantioselective TDM of ESL (using S-Lic concentrations). A chiral high-performance liquid chromatography assay with ultraviolet detection (HPLC-UV) previously developed and validated by our research group was used. Twenty-four patients admitted to the Coimbra University Hospital and supposedly receiving CBZ long-term treatment were identified. Blood samples were collected from patients and serum CBZ concentrations were measured by the usual TDM protocol. Aliquots of plasma from such patients were also submitted to a chiral HPLC-UV analysis. The bioanalytical data indicated that S-Lic and R-Lic were not present at detectable concentrations in plasma samples of the CBZ-treated patients. The chromatograms generated by the analysis of patient plasma samples, when compared with those obtained from blank plasma samples spiked with S-Lic and R-Lic, clearly showed the absence of interferences at the retention times of both Lic enantiomers. These data support the usefulness of the chiral HPLC-UV method used for the enantioselective TDM of ESL (using S-Lic) for programs in which switching from CBZ to ESL is implemented.