Pharmacokinetic Simulation and Area under the Curve Estimation of Drugs Subject to Enterohepatic Circulation.

Enterohepatic circulation (EHC) is a complex process where drugs undergo secretion and reabsorption from the intestinal lumen multiple times, resulting in pharmacokinetic profiles with multiple peaks. The impact of EHC on area under the curve (AUC) has been a topic of extensive debate, questioning the suitability of conventional AUC estimation methods. Moreover, a universal model for accurately estimating AUC in EHC scenarios is lacking. To address this gap, we conducted a simulation study evaluating five empirical models under various sampling strategies to assess their performance in AUC estimation. Our results identify the most suitable model for EHC scenarios and underscore the critical role of meal-based sampling strategies in accurate AUC estimation. Additionally, we demonstrate that while the trapezoidal method performs comparably to other models with a large number of samples, alternative models are essential when sample numbers are limited. These findings not only illuminate how EHC influences AUC but also pave the way for the application of empirical models in real-world drug studies.

Estimation of the Difference in Colistin Plasma Levels in Critically Ill Patients with Favorable or Unfavorable Clinical Outcomes.

In recent decades, antimicrobial resistance (AMR) has led to an increased use of therapeutic alternatives. Among these options, colistin continues to be an option for the treatment of multi-resistant (MDR) Gram-negative bacterial infections. However, due to its high toxicity (nephrotoxicity and neurotoxicity) and narrow therapeutic window, colistin treatment must be utilized carefully. Colistin-treated patients have been observed to have higher mortality due to inadequate therapeutic levels. The objective of this study was to estimate the difference in colistin plasma levels in critically ill patients, and its relationship to favorable or unfavorable clinical outcomes. This prospective observational study was conducted between September 2017 and June 2020 at the Universidad de La Sabana Clinic, in patients who had been treated with colistimethate sodium (CMS) for at least 72 h until day 7 of drug treatment in the critical care unit of a university hospital. There were no statistically significant differences in colistin levels between groups with favorable or unfavorable clinical outcomes (0.16 SD vs. 0.54 SD p-value = 0.167). There was higher mortality in patients with subtherapeutic levels (18% vs. 0%), and additionally, there was a greater rate of renal failure in the group with higher therapeutic levels (50% vs. 20.7%). Due to the loss of power of the study, we were unable to demonstrate a possible difference between colistin levels related to favorable or unfavorable clinical outcomes at day 7. However, we recommend further studies to evaluate the impact of measuring levels in terms of mortality and security.

Impact on Antibiotic Resistance, Therapeutic Success, and Control of Side Effects in Therapeutic Drug Monitoring (TDM) of Daptomycin: A Scoping Review.

Antimicrobial resistance (AR) is a problem that threatens the search for adequate safe and effective antibiotic therapy against multi-resistant bacteria like methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococci (VRE) and Clostridium difficile, among others. Daptomycin is the treatment of choice for some infections caused by Gram-positive bacteria, indicated most of the time in patients with special clinical conditions where its high pharmacokinetic variability (PK) does not allow adequate plasma concentrations to be reached. The objective of this review is to describe the data available about the type of therapeutic drug monitoring (TDM) method used and described so far in hospitalized patients with daptomycin and to describe its impact on therapeutic success, suppression of bacterial resistance, and control of side effects. The need to create worldwide strategies for the appropriate use of antibiotics is clear, and one of these is the performance of therapeutic drug monitoring (TDM). TDM helps to achieve a dose adjustment and obtain a favorable clinical outcome for patients by measuring plasma concentrations of an administered drug, making a rational interpretation guided by a predefined concentration range, and, thus, adjusting dosages individually.

Personalized Medicine for Antibiotics: The Role of Nanobiosensors in Therapeutic Drug Monitoring.

Due to the high bacterial resistance to antibiotics (AB), it has become necessary to adjust the dose aimed at personalized medicine by means of therapeutic drug monitoring (TDM). TDM is a fundamental tool for measuring the concentration of drugs that have a limited or highly toxic dose in different body fluids, such as blood, plasma, serum, and urine, among others. Using different techniques that allow for the pharmacokinetic (PK) and pharmacodynamic (PD) analysis of the drug, TDM can reduce the risks inherent in treatment. Among these techniques, nanotechnology focused on biosensors, which are relevant due to their versatility, sensitivity, specificity, and low cost. They provide results in real time, using an element for biological recognition coupled to a signal transducer. This review describes recent advances in the quantification of AB using biosensors with a focus on TDM as a fundamental aspect of personalized medicine.

Is There a Role for the Therapeutic Drug Monitoring of Colistin? An Overview.

Colistin is used as a last-line antibiotic for the treatment of Gram-negative multiresistant bacteria. Due to its high nephrotoxicity, Therapeutic Drug Monitoring (TDM) is recommended for dose adjustment. We aimed to evaluate the available evidence of TDM in patients given colistin to treat Gram-negative infections. In this paper, we offer an overview, using an electronic search of the literature (published up to June 2019, without language restrictions) that compares the clinical outcomes and measurements of colistin TDM. Ultimately, the Therapeutic Drug Monitoring (TDM) of colistin in Plasma could prevent nephrotoxicity risk.

Optical Biosensors for Therapeutic Drug Monitoring.

Therapeutic drug monitoring (TDM) is a fundamental tool when administering drugs that have a limited dosage or high toxicity, which could endanger the lives of patients. To carry out this monitoring, one can use different biological fluids, including blood, plasma, serum, and urine, among others. The help of specialized methodologies for TDM will allow for the pharmacodynamic and pharmacokinetic analysis of drugs and help adjust the dose before or during their administration. Techniques that are more versatile and label free for the rapid quantification of drugs employ biosensors, devices that consist of one element for biological recognition coupled to a signal transducer. Among biosensors are those of the optical biosensor type, which have been used for the quantification of different molecules of clinical interest, such as antibiotics, anticonvulsants, anti-cancer drugs, and heart failure. This review presents an overview of TDM at the global level considering various aspects and clinical applications. In addition, we review the contributions of optical biosensors to TDM.

An Approach to Measuring Colistin Plasma Levels Regarding the Treatment of Multidrug-Resistant Bacterial Infection.

Antimicrobial resistance to antibiotic treatment has significantly increased during recent years, causing this to become a worldwide public health problem. More than 70% of pathogenic bacteria are resistant to at least one of the currently used antibiotics. Polymyxin E (colistin) has recently been used as a "last line" therapy when treating Gram-negative multi-resistant bacteria. However, little is known about these molecules' pharmacological use as they have been discontinued because of their high toxicity. Recent research has been focused on determining colistimethate sodium's pharmacokinetic parameters to find the optimal dose for maintaining a suitable benefit-risk balance. This review has thus been aimed at describing the use of colistin on patients infected by multi-drug resistant bacteria and the importance of measuring this drug's plasma levels in such patients.

Label-Free Quantification of Anti-TNF-α in Patients Treated with Adalimumab Using an Optical Biosensor.

This study describes the development of an immunosensory label-free quantification methodology based on surface plasmon resonance (SPR) and its applicability in measuring/evaluating therapeutic drug monitoring (TDM) of anti-TNF-α monoclonal antibody (adalimumab) in rheumatoid arthritis (RA) patients. The experimental parameters evaluated in this study were immobilising ligands by pre-concentration assays, sensor surface regeneration, ascertaining the method's sensitivity and correlating the results from quantifying plasma samples by ELISA immunoassay. The results showed that TNF-α quantification values (in RU) were significantly different when comparing patients (~50-250 RU) to controls (~10-20 RU). Likewise, there was 0.97 correlation for patients and 0.91 for healthy volunteers using SPR and ELISA comparison methodologies. SPR immunosensory detection provided a precise, sensitive strategy, along with real-time determination, for quantifying adalimumab, having great potential for clinical routine regarding TDM.