Deep eutectic solvents (DESs) are a relatively new type of solvent that have attracted the attention of the scientific community due to their environmentally friendly properties and their versatility in many applications. Many possible DESs have been described and, thus, it is not easy to unequivocally characterize and generalize their properties. This is especially important in the case of the (eco)toxicity information that can be found for these mixtures. In this review, we collect data on the human and environmental toxicity of DESs, with the aim of gathering and exploring the behavioral patterns of DESs. The toxicity data found were analyzed attending to different factors: hydrogen bond donors or acceptors that form part of the eutectic mixture, pH, and the presence of organic acids in the DES molar ratio of the components, or interactions with natural compounds. In the case of ecotoxicity, results generally depend on the biomodel studied, along with other factors that have been also revised. Finally, we also carried out a revision of the biodegradation of DESs.

Therapeutic Deep Eutectic Systems (THEDESs) are a mixture of components, including an active pharmaceutical ingredient, that have recently emerged because of their interesting properties for drug therapies. In general, they have been recognized to increase the solubility and permeability of some drugs, and consequently, their bioavailability. Moreover, they have also been used for novel formulations of pharmaceuticals. Despite the potential benefits of THEDESs, concerns about their safety and toxicity remain. In this review, we summarize previous studies that have investigated the toxicity of THEDESs. These studies evaluate the toxicity of THEDESs using various methods, including cell cultures, animal models, and human trials. The results of previous findings suggest that THEDESs are generally well-tolerated and have low toxicity. However, further research is needed to fully understand the long-term effects of these systems on human health and to identify any potential adverse effects.

Tacrolimus (TAC) is a narrow-therapeutic-range immunosuppressant drug used after organ transplantation. A therapeutic failure is possible if drug levels are not within the therapeutic range after the first year of treatment. Pharmacogenetic variants and drug–drug interactions (DDIs) are involved. We describe a patient case of a young man (16 years old) with a renal transplant receiving therapy including TAC, mycophenolic acid (MFA), prednisone and omeprazole for prophylaxis of gastric and duodenal ulceration. The patient showed great fluctuation in TAC blood concentration/oral dose ratio, as well as pharmacotherapy adverse effects (AEs) and frequent diarrhea episodes. Additionally, decreased kidney function was found. A pharmacotherapeutic follow-up, including pharmacogenetic analysis, was carried out. The selection of the genes studied was based on the previous literature (CYP3A5, CYP3A4, POR, ABCB1, PXR and CYP2C19). A drug interaction with omeprazole was reported and the nephrologist switched to rabeprazole. A lower TAC concentration/dose ratio was achieved, and the patient’s condition improved. In addition, the TTT haplotype of ATP Binding Cassette Subfamily B member 1 (ABCB1) and Pregnane X Receptor (PXR) gene variants seemed to affect TAC pharmacotherapy in the studied patient and could explain the occurrence of long-term adverse effects post-transplantation. These findings suggest that polymorphic variants and co-treatments must be considered in order to achieve the effectiveness of the immunosuppressive therapy with TAC, especially when polymedicated patients are involved. Moreover, pharmacogenetics could influence the drug concentration at the cellular level, both in lymphocyte and in renal tissue, and should be explored in future studies.

Managing schizophrenia with clozapine poses a significant challenge due to prevalent therapeutic failures. The increasing interest in personalized medicine underscores the importance of integrating pharmacogenetic information for effective pharmacotherapeutic monitoring in patients. The objective of this study was to explore the correlation between DRD2, HTR2A, SLC6A4, CYP1A2, and ABCB1 polymorphisms and clozapine response in 100 patients with Treatment-Resistant Schizophrenia. Different scales such as the Positive and Negative Syndrome Scale (PANSS), the Warwick-Edinburgh Mental Wellbeing Scale (SWEMWBS), the Global Assessment of Functioning Scale (GAF), the Brief Negative Symptom Scale (BNSS), and pharmacokinetic parameters were used to analyse the efficacy of the treatment. Patients who exclusively responded to clozapine compared to the patients with augmentation strategies exhibited distinctive features, such as lower doses, plasma levels, and presented less-pronounced symptomatology. Genetic associations were explored, highlighting SLC6A4, HTR2A, and the *1F/*1F polymorphism for the CYP1A2 gene.

Tacrolimus (TAC) is a commonly used immunosuppressive drug in solid organ transplantation. Pharmacogenetics has been demonstrated before to be decisive in TAC pharmacotherapy. The CYP3A5*3 variant has been reported to be the main determinant of TAC dose requirements; however, other polymorphisms have also proven to be influential, especially in CYP3A5 non-expressor patients. The aim of this study is to evaluate the influence of genetic polymorphisms in TAC therapy in a cohort of Spanish transplant recipients. Genetic analysis including ten polymorphic variants was performed, and demographic and clinical data and pharmacotherapy of 26 patients were analyzed. No significant differences were found in weight-adjusted dose between CYP3A5 expressors and non-expressors (0.047 mg/kg vs. 0.044 mg/kg), while they were found for carriers of the CYP3A4*1B allele (0.101 mg/kg; p < 0.05). The results showed that patients with at least one CYP3A4*1B allele had a higher TAC dose and lower blood concentration. Dose-adjusted TAC blood levels were also lower in CYP3A4*1B carriers compared to non-carriers (0.72 ng/mL/mg vs. 2.88 ng/mL/mg). These results support the independence of CYP3A5*3 and CYP3A4*1B variants as determinants of dose requirements despite the linkage disequilibrium present between the two. The variability in genotype frequency between ethnicities may be responsible for the discrepancy found between studies.

Aim: Tuberous sclerosis complex (TSC) is a rare disease that produces multisystemic disorders. Everolimus (EVR) is the only immunosuppressive drug approved to control the symptoms and progression o... Tweetable abstract A pharmacogenetic study in pediatric sclerosis tuberous patients within everolimus therapy is presented. Polymorphisms involving CYP3A4 gene were associated with pharmacokinetics... Graphical abstract