scholarly journals Failure of Achieving Tacrolimus Target Blood Concentration Might Be Avoided by a Wide Genotyping of Transplanted Patients: Evidence from a Retrospective Study

2020 ◽  
Vol 10 (2) ◽  
pp. 47
Author(s):  
Giovanni Pallio ◽  
Natasha Irrera ◽  
Alessandra Bitto ◽  
Federica Mannino ◽  
Letteria Minutoli ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Side Effects ◽  
Therapeutic Drug Monitoring ◽  
Therapeutic Range ◽  
Independent Predictor ◽  
National Health System ◽  
Therapeutic Drug ◽  
Blood Levels ◽  
Wild Type ◽  
Tacrolimus Pharmacokinetics

Precise tacrolimus treatment in transplanted patients is achieved in the clinical setting by performing therapeutic drug monitoring (TDM) and consequently adjusting therapy. The aim of this study was to retrospectively analyze the variability in tacrolimus blood levels throughout 2 years of observation in 75 transplanted patients and to investigate if tacrolimus blood levels correlate with presence of genetic polymorphisms, thus modifying tacrolimus pharmacokinetics. CYP3A5*1 (G6986A), CYP3A4*1B (A392G), CYP3A4*22, ABCB1 (C3435T; C1236T; G2677A/T), SLCO1B1 (T521C), polymorphisms were analyzed. Based on the effect of their genotypes, patients were stratified into 5 groups: (1) reduced tacrolimus metabolism (RM), (2) increased metabolism (IM), (3) transporters polymorphisms (TM), (4) metabolism and transporter polymorphisms (AM) and (5) no mutations (Wild Type, WT). The percentage of the samples out of therapeutic range was significantly higher in the IM group than in the WT group (p = 0.001), as well as compared to the TM group (p = 0.004). Only IM pattern (p = 0.015) resulted as an independent predictor of number of tacrolimus blood levels out of therapeutic range. RM pattern (p = 0.006) was inversely related to the administered dose. Therefore, genotyping could become a standard practice before tacrolimus prescription thus decreasing side effects, increasing efficacy and reducing the economic burden for the national health system.

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

Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 263
Author(s):  
Carolina Osorio ◽  
Laura Garzón ◽  
Diego Jaimes ◽  
Edwin Silva ◽  
Rosa-Helena Bustos
Keyword(s):  
Side Effects ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Bacterial Resistance ◽  
Plasma Concentrations ◽  
Resistant Bacteria ◽  
Therapeutic Drug ◽  
Therapeutic Success ◽  
Favorable Clinical Outcome ◽  
And Control

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.

scholarly journals pH-mediated molecular differentiation for fluorimetric quantification of chemotherapeutic drugs in human plasma

2017 ◽  
Author(s):  
Luis A Serrano ◽  
Ye Yang ◽  
Elisa Salvati ◽  
Francesco Stellacci ◽  
Silke Krol ◽  
...  
Keyword(s):  
Side Effects ◽  
Therapeutic Drug Monitoring ◽  
Human Plasma ◽  
Active Metabolite ◽  
Drug Dosage ◽  
Therapeutic Drug ◽  
Chemotherapeutic Drugs ◽  
Molar Ratios ◽  
Simultaneous Quantification ◽  
Molecular Differentiation

At present, drug dosage is based on standardised approaches that disregard pharmakokinetic differences between patients and lead to non-optimal efficacy and unnecessary side effects. In this work, we demonstrate the potential of pH-mediated fluorescence spectroscopy for therapeutic drug monitoring in complex media. We apply this principle to the simultaneous quantification of the chemotherapeutic prodrug Irinotecan and its active metabolite SN-38 from human plasma across the clinically relevant concentration range, i.e. from micromolar to nanomolar at molar ratios of up to 30:1.

scholarly journals Optimum Use of Therapeutic Drug Monitoring and Pharmacokinetics-Pharmacodynamics in the NICU

2009 ◽  
Vol 14 (2) ◽  
pp. 66-74
Author(s):  
Peter Gal
Keyword(s):  
Drug Therapy ◽  
Therapeutic Drug Monitoring ◽  
Antiepileptic Drugs ◽  
Therapeutic Range ◽  
Drug Monitoring ◽  
Population Based ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Patient Response ◽  
Drug Concentrations

Therapeutic drug monitoring is increasingly giving way to dosing drugs based on population-based pharmacokinetic parameters, even when pharmacokinetic values vary quite a bit in individual patients. Further, drug concentrations are often considered appropriate if they are within a defined therapeutic range, even if the patient response is suboptimal. This lecture discusses the limitations of therapeutic ranges in neonates, and proposes greater emphasis on pharmacodynamic curves to individualize drug therapy. Examples are provided using methylxanthines, indomethacin, antiepileptic drugs and aminoglycosides. The potential to use pharmacokinetic findings to describe physiologic changes and occasionally assist with diagnosis is also discussed.

scholarly journals Therapeutic Drug Monitoring of Voriconazole in AIDS Patients

2021 ◽  
Author(s):  
Tingting Chen ◽  
Zhiqiang Lin ◽  
Huatang Zhang ◽  
Qingquan Zhang ◽  
Limian Hong ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Interactions ◽  
Therapeutic Range ◽  
Trough Concentration ◽  
Drug Monitoring ◽  
Linear Regression Analysis ◽  
Immune Deficiency Syndrome ◽  
Therapeutic Drug ◽  
Affecting Factors ◽  
Aids Patients

Abstract Background The safety and efficacy of Voriconazole in Acquired Immune Deficiency Syndrome (AIDS) patients is difficult to guarantee. In this study, Therapeutic Drug Monitoring (TDM) of Voriconazole in AIDS patients was investigated with the aim to further verify the significance of voriconazole TDM in AIDS patients and to explore more strategies to improve individualized medication. Methods The data of AIDS patients who underwent voriconazole TDM in our hospital from May 2018 to August 2021 were collected. The basic information of patients, the results of voriconazole TDM, the individualized intervention, the affecting factors of voriconazole concentration were analyzed, as well as the relationship between voriconazole trough concentration and safety. Results A total of 46 tests of voriconazole TDM were performed in 28 AIDS patients. Only 57.14% patients reached the therapeutic range at first TDM, and 87.50% patients reached the therapeutic range after intervention based on first TDM. 21.43% patients develop voriconazole-related Adverse Drug Reactions (ADRs), and ADRs were mostly occurred when voriconazole concentration is above 5.0 µg/mL. Spearman correlation coefficient rs was calculated to be 0.729 for voriconazole trough concentration and the incidence of ADRs, exhibiting a significant, positive linear correlation (P=0. 017). 50% patients had polypharmacy and drug interactions are common. For example, rifampicin can significantly reduce the plasma concentration of voriconazole. Multiple linear regression analysis showed Hypoproteinemia was a significant factor affecting voriconazole trough concentration(P=0.006). Conclusion AIDS patients usually have a low attainment rate of voriconazole trough concentration after initiation of standard dosing regimen. The affecting factors seem multifactorial and complex, of which hypoproteinemia is of great significance. Meanwhile, we need to be alert to the effects of drug interactions. The incidence of voriconazole related ADRs is high, mostly occurring when voriconazole concentration is above 5.0 µg/mL. Therefore, TDM can provide meaningful guidance for dosage optimization of voriconazole, and the dosage adjustment method in Chinese Guideline is applicable for the population of AIDS patients.

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