RESUMO
The French Society of Clinical Biology (SFBC) set up a working group "Biochemical markers of Covid-19" whose main objective is to review, analyse and monitor biological prescriptions according to the patient's care path. This study covers all public and private sectors of medical biology in metropolitan France and overseas and extends to the French-speaking world. We present a summary of feedbacks after 2 years of the pandemic. At the early stage of Covid-19, with regard to the regions surveyed, a common symptomatology with local zoonosis (dengue fever, zika, malaria, leptospirosis, etc.) complicates the diagnosis of Covid-19. At a more advanced stage, it is a question of managing an influx of patients suffering from acute respiratory distress syndrome. In this case, the biology is then simpler and delocalized medical biology devices have proven their effectiveness. As a result, ICU clinicians can better manage the frequent comorbidities encountered in these regions: obesity, diabetes, chronic renal failure, cardiovascular diseases.
La Société française de biologie clinique (SFBC) a mis en place un groupe de travail « Marqueurs biochimiques de Covid-19 ¼ dont l'objectif principal est de revoir, d'analyser et de suivre les prescriptions biologiques en fonction du parcours de soins du patient. Cette étude couvre tous les secteurs publics et privés de la biologie médicale en métropole et en Outre-mer et s'étend à la Francophonie. Nous présentons une synthèse des retours d'expériences après 2 ans de pandémie. Au stade précoce de la Covid-19, pour les régions interrogées, une symptomatologie commune avec des zoonoses locales (dengue, zika, paludisme, leptospirose ) complique le diagnostic de la Covid-19. À un stade plus avancé, il s'agit de gérer un afflux de patients atteints de syndrome de détresse respiratoire aiguë. La biologie est alors plus simple, et les dispositifs de biologie médicale délocalisée ont prouvé leur efficacité. De ce fait, les réanimateurs peuvent mieux gérer les comorbidités fréquentes rencontrées dans ces régions : obésité, diabète, insuffisance rénale chronique ou maladies cardiovasculaires.
Assuntos
COVID-19 , Falência Renal Crônica , Infecção por Zika virus , Zika virus , Animais , COVID-19/epidemiologia , Retroalimentação , Humanos , Pandemias , ZoonosesRESUMO
Tacrolimus presents high intra and inter-individual variability in its blood trough concentration (Cmin). Knowledge of the factors that are involved in tacrolimus Cmin variability is thus clinically important to prevent or limit it. Inflammation can affect the pharmacokinetic properties of drugs. We evaluated the contribution of acute inflammation in the pharmacokinetic variability of tacrolimus blood Cmin in a large cohort of liver transplant patients. Demographic, biological, and clinical data from 248 liver transplant patients treated with tacrolimus from January 2010 to December 2016 were retrospectively collected from medical records. In total, 1573 Cmin/dose and concomitant C-reactive protein (CRP) measurements were analysed. In multivariate analysis, the log Cmin/dose of tacrolimus was significantly and positively associated with the hematocrit, ALAT, and CRP concentrations. CRP concentrations were higher (p = 0.003) for patients with tacrolimus overexposure (i.e., tacrolimus Cmin > 15 µg/L) (median CRP (10th-90th percentiles): 27 mg/L (3-149 mg/L), n = 91) than they were for patients with a tacrolimus Cmin ≤ 15 µg/L (13 mg/mL (3-95 mg/L), n = 1482)). CRP in the fourth quartile (49 to 334 mg/L) was associated with a 2.6-fold increased risk of tacrolimus Cmin overexposure. Our study provides evidence that inflammation contributes to tacrolimus Cmin variability and suggests that inflammation should be considered for the correct interpretation of tacrolimus blood concentration.
RESUMO
Tacrolimus is the cornerstone of immunosuppressive therapy in solid organ transplantation and its blood concentrations are routinely monitored. Tacrolimus is extensively metabolized into metabolites that are supposed to be nephrotoxic. Yet, few analytical methods have been described to simultaneously quantify tacrolimus and its main metabolites. We developed and validated a simple liquid chromatography-mass spectrometry method for the quantification of tacrolimus and its three desmethylated metabolites, 13-O, 15-O, and 31-O-desmethylated tacrolimus (M-I, M-III, and M-II respectively) in human whole blood. Protein precipitation of 50 µL of whole blood with 100 µL methanol and zinc sulfate was used as a single-extraction procedure. Tacrolimus and its metabolites were quantified using electrospray ionization-triple quadrupole mass spectrometry in combination with selected reaction monitoring detection in the positive ionization mode. The method was validated following FDA recommendations. This method was precise (intra- and inter-assay coefficients of variation: 2.88-7.81% and 3.96-12.10% for low and high levels of internal quality controls, respectively) and accurate (intra- and inter-assay biases: -1.67-10.30%, and -0.77--9.36%, respectively). In adult kidney transplant patients who were treated with tacrolimus prolonged release formulation, the median (10th-90th percentiles) trough concentrations (n = 16) of tacrolimus, M-I, and M-III were 5.85 (3.37-7.09), 0.100 (0.037-0.168), 0.051 (0.03-0.104), respectively. M-II was measured in only 2 trough samples. The metabolic ratios M-I/tacrolimus and M-III/tacrolimus were 0.017 (0.009-0.027) and 0.009 (0.006-0.015) when measured on trough concentration and 0.022 (0.011-0.037) and 0.008 (0.006-0.015) when measured on area under the curves 0-24 h. This method is a suitable and easy-to-perform tool for future pharmacokinetic-pharmacodynamics studies investigating the importance of tacrolimus and its metabolites blood exposure for solid organ graft survival.
RESUMO
The knowledge of factors of pharmacokinetic variability is important in order to personalize pharmacological treatment, particularly for drugs with a narrow therapeutic range for which pharmacological therapeutic monitoring is recommended. Inflammation is a protective response against acute infections and injuries that contributes to intra- and inter-individual variability in drug exposure by modulating the activity of enzymes involved in drug metabolism, and by altering the binding of drugs to plasma proteins. The understanding of the impact of inflammation on drug metabolism and the related clinical consequences allow to better take into consideration the effect of inflammation on the variability of drug exposure. We first summarized the molecular mechanisms by which inflammation contributes to the inhibition of drug metabolism enzymes. We then presented an updated overview of the consequences of the outcome of acute infectious event on pharmacokinetic exposure of drugs with a narrow therapeutic range and that are substrates of cytochrome P450, and the related clinical consequences. Finally, in the context of the COVID-19 pandemic, we reported examples of drug overexposures in COVID- 19 infected patients.
