scholarly journals Therapeutic Drug Monitoring of Vancomycin in Patients with Altered Pharmacokinetics: A Narrative Review on Pharmacokinetic Assessments

2021 ◽  
Author(s):  
Parisa Ghasemiyeh ◽  
Afsaneh Vazin ◽  
Soliman Mohammadi-Samani
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Bacterial Infections ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Morbidly Obese ◽  
Renal Elimination ◽  
Advantages And Disadvantages ◽  
Hospitalization Period ◽  
Altered Pharmacokinetic

Introduction: Vancomycin is a glycopeptide antibiotic that is considered as the drug of choice against many Gram-positive bacterial infections, especially Methicillin-resistant Staphylococcus aureus (MRSA). Also, it is a hydrophilic drug with predominantly renal elimination. Given the vancomycin narrow therapeutic index, therapeutic drug monitoring (TDM) is essential to achieve an optimum clinical response and avoid vancomycin-induced adverse drug reactions including nephrotoxicity and ototoxicity. Although different studies are available on vancomycin pharmacokinetic assessment and vancomycin TDM, still there are controversies regarding the selection among different pharmacokinetic parameters including trough concentration (Cmin), the daily area under the curve to minimum inhibitory concentration (AUC24h/MIC) ratio, AUC of intervals (AUCτ), elimination constant (k), vancomycin clearance (ClV) and methods of their calculations for TDM purposes. Methods: In this review, different pharmacokinetic parameters for vancomycin TDM have been discussed in detail along with corresponding advantages and disadvantages, based on the literature review. Determination of vancomycin concentration at steady state (Css) during 24h continuous injection are mentioned. Also, vancomycin pharmacokinetic assessments are discussed in detail in patients with altered pharmacokinetic parameters including those with renal and/or hepatic failure, critically ill patients, patients with burn injuries, intravenous (IV) drug users, obese and morbidly obese patients, those with cancer, patients undergoing organ transplantation, and vancomycin administration during pregnancy and lactation. Results and Discussion: An individualized dosing regimen is required to guarantee the optimum therapeutic results and minimize severe adverse reactions such as acute kidney injury (AKI) in these special groups of patients with altered pharmacokinetic parameters. Also, according to the pharmacoeconomic data on vancomycin TDM, pharmacokinetic assessments would be cost-effective in the mentioned groups of patients with altered pharmacokinetics and associated with shorter hospitalization period, faster clinical stability status, and shorter courses of inpatient vancomycin administration.

scholarly journals Therapeutic Drug Monitoring of Protein Unbound Ciprofloxacin Concentrations to avoid inadequate Treatment of severe Bacterial Infections in Critically ill Patients

2018 ◽  
Vol 4 (5) ◽  
pp. 166-174
Author(s):  
Nora J mabelis ◽  
Kimberly N. Shudofsky ◽  
Joost J. van Raaij ◽  
Sjoerd D. Meenks ◽  
Thomas Havenith ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Critically Ill ◽  
Drug Monitoring ◽  
Critically Ill Patients ◽  
Bacterial Infections ◽  
Therapeutic Drug

Population Pharmacokinetics of Meropenem in Preterm Infants

2021 ◽  
Vol 76 (5) ◽  
pp. 497-505
Author(s):  
Irina B. Bondareva ◽  
Sergey K. Zyryanov ◽  
Aleksandra M. Kazanova
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Pharmacokinetic Parameter ◽  
Gestational Age ◽  
Drug Monitoring ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Variability ◽  
Older Children ◽  
Term Neonates

Background. Meropenem, a broad spectrum carbapenem antibiotic, is often used for newborns despite of limited data available on neonatal pharmacokinetics. Due to pharmacokinetic and pharmacodynamic differences as well as to significant changes in the human body related to growth and maturation of organs and systems, direct scaling and dosing extrapolation from adults or older children with adjustment on patients weight can result in increased risk of toxicity or treatment failures. Aims to evaluate the pharmacokinetics of meropenem in premature neonates based on therapeutic drug monitoring data in real clinical settings. Materials. Of 53 pre-term neonates included in the pharmacokinetic/pharmacodynamic analysis, in 39 (73.6%) patients, gestational age ranged from 23 to 30 weeks. Population and individual pharmacokinetic parameter values were estimated by the NPAG program from the Pmetrics package based on peak-trough therapeutic drug monitoring. Samples were assayed by high-performance liquid chromatography. One-compartment pharmacokinetic model with zero-order input and first-order elimination was used to fit concentration data and to predict pharmacokinetic parameter (%T MIC of free drug) for virtual patients with simulated fast, moderate and slow meropenem elimination received different dosage by minimum inhibitory concentration (MIC) level. Univariate and multivariate regression analysis was used to evaluate the influence of patients covariates (gestational age, postnatal age, postconceptual age, body weight, creatinine clearance calculated by Schwartz formula, etc) on estimated meropenem pharmacokinetic parameters. Results. The identified population pharmacokinetic parameters of meropenem in pre-term newborns (elimination half-lives T1/2 = 1.93 0.341 h; clearance CL = 0.26 0.085 L/h/ kg; volume of distribution V = 0.71 0.22 L/h) were in good agreement with those published in the literature for adults, neonates and older children. Pharmacokinetic/pharmacodynamic modeling demonstrated that a meropenem dosage regimen of 90 mg/kg/day administered using prolonged 3-hour infusion every 8 hours should be considered as potentially effective therapy if nosocomial infections with resistant organisms (MIC 8 mg/L) are treated. Conclusions. Neonates and especially pre-term neonates have a great pharmacokinetic variability. Meropenem dosing in premature newborns derived from population pharmacokinetic/pharmacodynamic model can partly overcome the variability, but not all pharmacokinetic variability can be explained by covariates in a model. Further personalizing based on Bayesian forecasting approach and a patients therapeutic drug monitoring data can help to achieve desired pharmacodynamic target.

Therapeutic Drug Monitoring in Neonates: Problems and Issues

1988 ◽  
Vol 22 (4) ◽  
pp. 317-323 ◽  
Author(s):  
Peter Gal
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Concentration ◽  
Drug Monitoring ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Plasma Drug ◽  
Potential Applications ◽  
Intensive Care Nursery ◽  
Effective Use ◽  
Selection Of

Therapeutic drug monitoring has been applied in several patient populations to promote safer, more effective use of drugs. The development of therapeutic ranges allows clinicians to aim for a plasma drug concentration that is usually safe and effective, and calculation of specific pharmacokinetic parameters allows selection of doses that will achieve the desired plasma concentration. This concept certainly holds true in the intensive care nursery; however, the intensity of monitoring in this setting provides opportunities for far broader application of the information obtained from drug concentration monitoring. This review provides an overview of the complexity of and potential applications for therapeutic drug monitoring in neonates based on literature and clinical experience.

Therapeutic Drug Monitoring of Vancomycin in a Morbidly Obese Patient

1998 ◽  
Vol 20 (3) ◽  
pp. 261-265 ◽  
Author(s):  
Scott R. Penzak ◽  
Paul O. Gubbins ◽  
Keith A. Rodvold ◽  
Steve L. Hickerson
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Obese Patient ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Morbidly Obese ◽  
Morbidly Obese Patient

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.

Therapeutic monitoring of methotrexate in chemotherapy

2017 ◽  
Vol 53 (4) ◽  
pp. 241-246
Author(s):  
Ewelina Szpak ◽  
Krzysztof Lewandowski ◽  
Robert Kowalski ◽  
Barbara Bogomas-Woźnicka ◽  
Ninela Irga-Jaworska
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Rescue Therapy ◽  
Elimination Rate ◽  
Toxic Effects ◽  
Therapeutic Monitoring ◽  
Therapeutic Drug ◽  
Cytostatic Drug ◽  
Renal Elimination ◽  
Forced Diuresis

Methotrexate is a cytostatic drug, folic acid antagonist, used in chemotherapy and immunosuppression in adults and in children. Its use in high doses is an absolute indication for therapeutic drug monitoring. Methotrexate is a highly toxic drug and requires dosage of specific antidote, calcium folinate. This rescue therapy helps to prevent methotrexate toxic effects and bone marrow suppression. Monitoring methotrexate concentration also helps to diagnose patients with decreased MTX elimination rate, who would benefit from glucarpidase treatment, an enzyme which degrades methotrexate molecules or theophylline, which is neuroprotective and increases renal elimination. Based on methotrexate serum concentration also time of forced diuresis and urine alkalinization is appointed in order to prevent acute nephrotoxicity. Of great importance is the fact that delayed elimination may be result of drug-drug interaction, part of which may be prevented. The purpose of this paper is to highlight the role of therapeutic drug monitoring in the prevention of methotrexate toxic effects.

Predictive Techniques Applied to Imipramine Therapeutic Drug Monitoring

DICP ◽  
1989 ◽  
Vol 23 (5) ◽  
pp. 389-394
Author(s):  
M. Mar Fernandez de Gatta ◽  
Milagros Tamayo ◽  
Maria José Garcia ◽  
Cristobal Montojo ◽  
J. Ramón Gutierrez ◽  
...  
Keyword(s):  
Steady State ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Prediction Error ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Serum Concentrations ◽  
Drug Concentrations ◽  
Steady State Serum

The aim of this study was to establish the performance of pharmacokinetic methods employing little data on serum drug concentrations obtained in routine therapeutic drug monitoring of imipramine. Forty-three and 123 serum levels were obtained in 8 adult depressive patients (aged 57–80 y) and 34 enuretic children (aged 5–13 y), respectively. Forecasting of the serum concentrations was performed based on mean population pharmacokinetic parameters (method A), with knowledge of one steady-state serum concentration (method B), and from two or more steady-state serum concentrations (method C). The accuracy and precision of each method were evaluated from the mean prediction error (ME) and from the root mean squared prediction error (RMSE), respectively. The values of ME and RMSE of methods B and C proved to be significantly lower than those found using method A. Method C was the most precise and accurate in both populations. Method A underestimates the serum concentrations observed in adults (ME >0) but overestimates them in children (ME <0), although to a lesser extent. The study shows that it is possible to obtain a good estimation of individual dosage needs from one or more serum concentrations obtained at steady state. Clinical application of these methods (B and C) yields an increase in the efficiency and safety of the treatment, particularly in special populations such as geriatric and pediatric patients.

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