scholarly journals Appropriate Use of Glycopeptide Antibiotics and Therapeutic Drug Monitoring for Invasive Infections

2021 ◽  
Vol 96 (6) ◽  
pp. 463-477
Author(s):  
Si-Ho Kim ◽  
Soo-Youn Lee ◽  
Cheol-In Kang
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Surrogate Marker ◽  
Therapeutic Drug ◽  
Glycopeptide Antibiotics ◽  
Time Curve ◽  
Bacteriological Response ◽  
Concentration Time ◽  
Invasive Infections ◽  
Gram Positive Cocci

Vancomycin and teicoplanin are representative glycopeptide antibiotics with activities against gram-positive cocci. The area under the drug concentration–time curve (AUC)/minimal inhibitory concentration (MIC) has been extensively used as an indicator of the bacteriological response to glycopeptide antibiotics, and the trough concentration has been used as a surrogate marker for the AUC/MIC. However, the guidelines for therapeutic drug monitoring (TDM) are being revised in accordance with increasing pharmacokinetic understanding of glycopeptide antibiotics. This review describes the pharmacokinetic/pharmacodynamic characteristics of glycopeptide antibiotics and discusses their optimal use with appropriate TDM.

scholarly journals Optimizing the Initial Amikacin Dosage in Adults

2015 ◽  
Vol 59 (11) ◽  
pp. 7094-7096 ◽  
Author(s):  
Bryan P. White ◽  
Ben Lomaestro ◽  
Manjunath P. Pai
Keyword(s):  
Body Weight ◽  
Standard Deviation ◽  
Therapeutic Drug Monitoring ◽  
Drug Concentration ◽  
Drug Monitoring ◽  
Maintenance Dose ◽  
Therapeutic Drug ◽  
High Dose ◽  
Time Curve ◽  
Concentration Time

ABSTRACTWe report on the pharmacokinetics (PK) and pharmacodynamics (PD) of high-dose (>15 mg/kg of body weight per day) amikacin. A mean (standard deviation [SD]) maximum drug concentration in the serum (Cmax) and 24-h area under the concentration-time curve (AUC24) of 101 (49.4) mg/liter and 600 (387) mg · h/liter, respectively, were observed (n= 73) with 28.0 (8.47) mg/kg/day doses. An initial amikacin dose of 2,500 mg in adults weighing 40 kg to 200 kg with therapeutic drug monitoring to adjust the maintenance dose will optimize its PK and PD.

Vancomycin Advanced Therapeutic Drug Monitoring: Exercise in Futility or Virtuous Endeavor to Improve Drug Efficacy and Safety?

2020 ◽  
Author(s):  
Thomas J Dilworth ◽  
Lucas T Schulz ◽  
Warren E Rose
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Inhibitory Concentration ◽  
Drug Efficacy ◽  
Therapeutic Drug ◽  
Limited Data ◽  
Considerable Effort ◽  
Time Curve ◽  
Concentration Time ◽  
High Level

Abstract Vancomycin is commonly prescribed to hospitalized patients. Decades of pharmacokinetic/pharmacodynamic research culminated in recommendations to monitor the ratio of the area under the concentration-time curve (AUC) to the minimum inhibitory concentration in order to optimize vancomycin exposure and minimize toxicity in the revised 2020 guidelines. These guideline recommendations are based on limited data without high-quality evidence and limitations in strength. Despite considerable effort placed on vancomycin therapeutic drug monitoring (TDM), clinicians should recognize that the majority of vancomycin use is empiric. Most patients prescribed empiric vancomycin do not require it beyond a few days. For these patients, AUC determinations during the initial days of vancomycin exposure are futile. This added workload may detract from high-level patient care activities. Loading doses likely achieve AUC targets, so AUC monitoring after a loading dose is largely unnecessary for broad application. The excessive vancomycin TDM for decades has been propagated with limitations in evidence, and it should raise caution on contemporary vancomycin TDM recommendations.

Influence of Infusion Methods on Therapeutic Drug Monitoring in Pediatric Patients

1986 ◽  
Vol 20 (5) ◽  
pp. 367-369 ◽  
Author(s):  
Milap C. Nahata ◽  
William J. Taylor
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Serum Concentration ◽  
Drug Monitoring ◽  
Pediatric Patients ◽  
Time Profile ◽  
Therapeutic Monitoring ◽  
Therapeutic Drug ◽  
Concentration Time ◽  
Infusion Method ◽  
Infusion System

The purpose of this article is to emphasize the importance of infusion method on therapeutic drug monitoring in pediatric patients. Although effective serum concentrations are anticipated after intravenous infusion of drugs, studies with chloramphenicol and tobramycin have shown that the infusion method can have a profound influence on peak serum concentration and time to achieve peak concentration during therapy. Factors including infusion rate, injection site, volume of drug and fluid to be infused in the tubing, and type of infusion system should be considered for accurate drug delivery. Specific guidelines for drug infusions should be available at each institution. Since serum concentration predictions are based on the dose infused and infusion time, meaningful therapeutic monitoring data can be generated only with the understanding of the influence of infusion method on serum concentration-time profile of drugs.

scholarly journals Evaluation of Saliva as a Potential Alternative Sampling Matrix for Therapeutic Drug Monitoring of Levofloxacin in Patients with Multidrug-Resistant Tuberculosis

2019 ◽  
Vol 63 (5) ◽  
Author(s):  
Samiksha Ghimire ◽  
Bhagwan Maharjan ◽  
Erwin M. Jongedijk ◽  
Jos G. W. Kosterink ◽  
Gokarna R. Ghimire ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Multidrug Resistant ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Time Curve ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Liquid Chromatography Tandem Mass ◽  
Mdr Tb

ABSTRACT Saliva may be a useful alternative matrix for monitoring levofloxacin concentrations in multidrug-resistant tuberculosis (MDR-TB) patients. The objectives of this study were (i) to evaluate the correlation between plasma and salivary levofloxacin (Lfx) concentrations in MDR-TB patients and (ii) to gauge the possibility of using saliva as an alternative sampling matrix for therapeutic drug monitoring of Lfx in areas where TB is endemic. This was a prospective pharmacokinetic study that enrolled MDR-TB patients receiving levofloxacin (750- to 1,000-mg once-daily dosing) under standardized treatment regimen in Nepal. Paired blood and saliva samples were collected at steady state. Lfx concentrations were quantified using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated using noncompartmental kinetics. Lfx drug exposures were evaluated in 23 MDR-TB patients. During the first month, the median (interquartile range [IQR]) areas under the concentration-time curve from 0 to 24 h (AUC0–24) were 67.09 (53.93 to 98.37) mg ⋅ h/liter in saliva and 99.91 (76.80 to 129.70) mg ⋅ h/liter in plasma, and the saliva plasma (S/P) ratio was 0.69 (0.53 to 0.99). Similarly, during the second month, the median (IQR) AUC0–24 were 75.63 (61.45 to 125.5) mg ⋅ h/liter in saliva and 102.7 (84.46 to 131.9) mg ⋅ h/liter in plasma, with an S/P ratio of 0.73 (0.66 to 1.18). Furthermore, large inter- and intraindividual variabilities in Lfx concentrations were observed. This study could not demonstrate a strong correlation between plasma and saliva Lfx levels. Despite a good Lfx penetration in saliva, the variability in individual saliva-to-plasma ratios limits the use of saliva as a valid substitute for plasma. Nevertheless, saliva could be useful in semiquantitatively predicting Lfx plasma levels. (This study has been registered at ClinicalTrials.gov under identifier NCT03000517.)

scholarly journals Therapeutic Drug Monitoring of Linezolid: a Retrospective Monocentric Analysis

2010 ◽  
Vol 54 (11) ◽  
pp. 4605-4610 ◽  
Author(s):  
Federico Pea ◽  
Mario Furlanut ◽  
Piergiorgio Cojutti ◽  
Francesco Cristini ◽  
Eleonora Zamparini ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
High Performance ◽  
Drug Exposure ◽  
Plasma Concentrations ◽  
Hplc Method ◽  
Therapeutic Drug ◽  
Time Curve ◽  
Standard Dosage ◽  
Wide Variability

ABSTRACT The objective of the present retrospective observational study carried out in patients receiving a standard dosage of linezolid and undergoing routine therapeutic drug monitoring (TDM) was to assess the interindividual variability in plasma exposure, to identify the prevalence of attainment of optimal pharmacodynamics, and to define if an intensive program of TDM may be warranted in some categories of patients. Linezolid plasma concentrations (trough [C min] and peak [C max] levels) were analyzed by means of a high-performance liquid chromatography (HPLC) method, and daily drug exposure was estimated (daily area under the plasma concentration-time curve [AUC24]). The final database included 280 C min and 223 C max measurements performed in 92 patients who were treated with the fixed 600-mg dose every 12 h (q12h) intravenously (n = 58) or orally (n = 34). A wide variability was observed (median values [interquartile range]: 3.80 mg/liter [1.75 to 7.53 mg/liter] for C min, 14.70 mg/liter [10.57 to 19.64] for C max, and 196.08 mg·h/liter [144.02 to 312.10 mg·h/liter] for estimated AUC24). Linezolid C min was linearly correlated with estimated AUC24 (r 2 = 0.85). Optimal pharmacodynamic target attainment (defined as C min of ≥2 mg/liter and/or AUC24/MIC90 ratio of >80) was obtained in about 60 to 70% of cases, but potential overexposure (defined as C min of ≥10 mg/liter and/or AUC24 of ≥400 mg·h/liter) was documented in about 12% of cases. A significantly higher proportion of cases with potential overexposure received cotreatment with omeprazole, amiodarone, or amlodipine. Our study suggests that the application of TDM might be especially worthwhile in about 30% of cases with the intent of avoiding either the risk of dose-dependent toxicity or that of treatment failure.

scholarly journals Therapeutic Drug Monitoring of Cytotoxic Drugs

2020 ◽  
Vol 10 (02) ◽  
pp. 284-291
Author(s):  
Qutaiba Ahmad Al Khames Aga ◽  
Yazan A. Bataineh ◽  
Hala Mousa Sbaih
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Malignant Tumors ◽  
Therapeutic Index ◽  
Review Article ◽  
Cytotoxic Drugs ◽  
Therapeutic Drug ◽  
Narrow Therapeutic Index ◽  
Time Curve ◽  
The Common

The majority of anticancer drugs are recognized with a narrow therapeutic index, the area under the plasma levels vs. time curve (AUC) is the common pharmacokinetic (PK) parameter, which utilizes specifically for cytotoxic drugs. Therapeutic drug monitoring (TDM) approach in these drugs has never been completely applied due to different reasons, for example, the use of combination chemotherapies for different malignant tumors, and the behavior of intracellular compounds; it is possible to eliminate these limitations by using specific concentrations of cytotoxic drugs and measure AUC after certain conditions. In this review article, we discussed the common TDM parameters, methods of analysis, and some of drug interactions for a group of cytotoxic drugs.

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