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Background: Hydroxyurea (HU), also known as hydroxycarbamide, is an oral ribonucleotide reductase inhibitor. In 1999, the United States Food and Drug Administration (FDA) approved HU for the treatment of sickle cell disease (SCD). Since then, it has become the cornerstone in the management of SCD patients, helping to reduce vaso-occlusive crises, acute chest syndrome, the need for blood transfusions, hospitalizations and mortality. There is considerable variability among individuals in HU pharmacokinetic (Pk) parameters that can influence treatment efficacy and toxicity. The objective of this work is part of a clinical study aimed at investigating HU Pk and determining the optimal sampling time to estimate the Area Under the Curve (AUC) in SCD patients. Methods: HU plasma concentration in 80 patients at various time points (2, 4, 6, 24 h) following a 48-h drug washout was quantified using High-Pressure Liquid Chromatography (HPLC) coupled with an ultraviolet (UV) detection method previously described in the literature and adapted to new conditions with partial modifications. Results: The mean HU administered dose was 19.5 ± 5.1 mg/kg (range: 7.7–37.5 mg/kg). The median AUC quantified in plasma patients was 101.3 mg/L/h (Interquartile Range (IQR): 72.5–355.9) and it was not influenced by the weight-based dose. However, there was a strong positive correlation between AUC and Body Mass Index (BMI) as well as dose per Body Surface Area (BSA). Along with a three-point approach for AUC determination present in the literature, we show results obtained from a four-point sampling strategy, which is more useful and effective for better optimizing dose escalation to the maximum tolerated dose (MTD). Moreover, we observed that most patients achieved the maximum HU plasma concentration two hours after drug administration, regardless of age differences. Conclusions: HU treatment, which represents a milestone in the treatment of SCD due to its ability to reduce disease complications and improve patients’ quality of life, requires careful monitoring to optimize the individual dose for saving potential side effects and/or adverse events.

Teicoplanin, a glycopeptide antibiotic commonly used to treat bacterial infections, was discovered to be active in vitro against SARS-CoV-2. The aim of this study was to assess the levels of teicoplanin and its components in a cohort of adult and pediatric SARS-CoV-2 patients, evaluating the effect of sex and age on analyte concentrations. The levels of AST, ALT and leukocytes were shown to be higher in females, while the C reactive protein was higher in males. Evaluating the absence/presence of teicoplanin isoforms, we observed that A2-2_3 is the only one consistently present in pediatrics and adults. In adult men and all pediatrics, A2-4_5 is always present. In pediatrics, except for A3-1, median isoform concentrations were higher in females; on the contrary, in adult patients, males showed higher levels. This is the first study to describe levels of teicoplanin isoforms in SARS-CoV-2 infected patients in males and females, and pediatrics and adults, despite the small sample size of our cohort. The observed results imply that additional testing, via therapeutic drug monitoring, may be helpful to more effectively manage infections, particularly those caused by the most recent viruses.

Com a endemia do vírus Sars-CoV-2, muitos indivíduos acometidos de doenças hepáticas preexistentes como cirrose hepática e as hepatopatias crônicas se tornaram expostos à descompensação do quadro pela virulência da exposição e à suscetibilidade individual pela infecção do novo coronavírus. A citotoxicidade direta do vírus Sars-CoV-2 ocorre pela sua replicação nas células hepáticas, dada pela ligação do agente às células-alvo pela expressão da enzima conversora de angiotensina 2 (ECA2), que é a principal mediadora da replicação viral nos pacientes infectados pela Covid-19. Como consequência, as citocinas pró-inflamatórias aumentam e podem provocar hipóxia e isquemia sistêmica. Em associação à linfopenia e à diminuição dos níveis de células T-CD4+, os pacientes podem evoluir para descompensação ou piora do quadro infeccioso, com a insuficiência hepática crônica agudizada desde a primeira semana e, assim, diminuição de sobrevida. Os pacientes pré-diagnosticados com cirrose e infectados pelo vírus da Covid-19 possuem maior acometimento hepático e pior prognóstico e, portanto, merecem acompanhamento especial, sendo cuidadosamente avaliados a fim de possibilitar a redução das lesões hepáticas causadas pela infecção.