Therapeutic monitoring of methotrexate in chemotherapy

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.

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Therapeutic Drug Monitoring: Psychotropic Drugs

Journal of Pharmacy Practice ◽

10.1177/089719008900200609 ◽

1989 ◽

Vol 2 (6) ◽

pp. 403-415 ◽

Cited By ~ 2

Author(s):

Randall D. Seifert

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Antipsychotic Drugs ◽

Practical Knowledge ◽

Therapeutic Monitoring ◽

Therapeutic Drug ◽

Clinical Use ◽

Careful Patient ◽

Recovery Expectations ◽

Positive Results

The therapeutic monitoring of patients who take antipsychotic drugs can be both challenging and rewarding. Antipsychotics have been in clinical use for over 30 years; yet, their complex pharmacology is not fully understood and parallels our infant knowledge of human brain chemistry. The art of successful therapeutic drug monitoring depends on the clinician's knowledge of basic pharmacology, an understanding of psychiatric disorders, and a sensitivity for careful patient observation. In addition, a thorough history, well thought out goals, and reasonable recovery expectations are essential. Antipsychotic drugs are never curative and should be used judiciously for indications where positive results outweigh the risks of adverse effects. This article will provide the reader with sound, practical knowledge of how to monitor these drugs in any clinical setting. © 1989 by W.B. Saunders Company.

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Evidence-based Implementation of Free Phenytoin Therapeutic Drug Monitoring

Clinical Chemistry ◽

10.1093/clinchem/46.8.1132 ◽

2000 ◽

Vol 46 (8) ◽

pp. 1132-1135 ◽

Cited By ~ 41

Author(s):

Martha Burt ◽

David C Anderson ◽

Julie Kloss ◽

Fred S Apple

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Medical Center ◽

Clinical Findings ◽

Therapeutic Monitoring ◽

Therapeutic Drug ◽

Clinical Indicator ◽

Interindividual Variations ◽

Data Points ◽

Pharmacologically Active

Abstract Background: The majority of laboratories measure total phenytoin concentration for therapeutic drug monitoring. However, there are substantial interindividual variations in free phenytoin concentrations, the pharmacologically active component. Methods: We describe the process and data used to implement monitoring of free phenytoin only in an urban medical center. Over a 6-week period, total and free phenytoin concentrations were measured, clinical charts reviewed, and indications for alterations in the percentage of free phenytoin fraction were determined. Results: Of the 189 phenytoin requests from 139 patients, 136 data points were analyzed. Free phenytoin concentrations were 6.8–35.3%, with 50% outside the expected range of 8–12%. Clinical indications likely responsible for variations were hypoalbuminemia, drug interactions, uremia, pregnancy, and age. Overall, 30% of patients demonstrated a discrepancy between therapeutic, subtherapeutic, or supratherapeutic concentrations between free and total phenytoin concentrations. The largest discordance (53%) occurred in the patient group with free phenytoin <8% or >12%. Conclusions: This study supports previous clinical findings that monitoring total phenytoin is not as reliable as free phenytoin as a clinical indicator for therapeutic and nontherapeutic concentrations. Thus, we recommend that therapeutic monitoring should use free phenytoin concentrations only.

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A Moving Target—Vancomycin Therapeutic Monitoring

Journal of the Pediatric Infectious Diseases Society ◽

10.1093/jpids/piaa078 ◽

2020 ◽

Vol 9 (4) ◽

pp. 474-478

Author(s):

Alaina N Burns ◽

Jennifer L Goldman

Keyword(s):

Clinical Practice ◽

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Clinical Care ◽

Area Under The Curve ◽

Therapeutic Monitoring ◽

Therapeutic Drug ◽

Moving Target ◽

Efficacy And Safety ◽

Vancomycin Trough

Abstract Therapeutic drug monitoring (TDM) has been a common practice to optimize efficacy and safety of vancomycin. While vancomycin trough-only TDM has widely been integrated into pediatric clinical practice since 2009, recently updated vancomycin TDM guidelines published in March 2020 recommend area under the curve (AUC) based TDM for vancomycin instead of trough-only TDM. In this review, we discuss the rationale behind the change in TDM recommendations, describe two approaches for calculating vancomycin AUC in clinical practice, and address considerations for integrating vancomycin AUC TDM into pediatric clinical practice. Our primary goal is to provide pediatric clinicians with a resource for implementing vancomycin AUC monitoring into clinical care.

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Plasma vs whole blood for therapeutic drug monitoring of patients receiving FK 506 for immunosuppression

Clinical Chemistry ◽

10.1093/clinchem/40.12.2247 ◽

1994 ◽

Vol 40 (12) ◽

pp. 2247-2253 ◽

Cited By ~ 45

Author(s):

M Winkler ◽

B Ringe ◽

J Baumann ◽

M Loss ◽

K Wonigeit ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Enzyme Immunoassay ◽

Drug Monitoring ◽

Whole Blood ◽

Plasma Concentrations ◽

Therapeutic Monitoring ◽

Therapeutic Drug ◽

Fk 506 ◽

Blood Samples ◽

The Matrix

Abstract By retrospective analysis of 13,000 blood samples obtained from 248 patients receiving FK 506 therapy, we compared the suitability of plasma with that of whole blood as the matrix for therapeutic drug monitoring of FK 506. The plasma concentrations did not correlate with the concentrations in whole blood (r = 0.56). In contrast to plasma samples (analyzed by enzyme immunoassay), FK 506 was detectable in all whole-blood samples (analyzed by enzyme immunoassay/microparticle enzyme immunoassay). The inter- and intraindividual variations of FK 506 measurements were greater in plasma than in whole blood. Moreover, plasma concentrations correlated only poorly with clinical events. There was a tendency to greater plasma concentrations being measured during episodes of toxicity, but no clear difference was evident between stable course and rejection. In whole-blood specimens, a correlation between reduced or increased FK 506 concentrations and rejection or toxicity, respectively, was observed. The discriminatory power of whole-blood values was greater for the differentiation between toxicity and stable course than between rejection and stable course. We therefore recommend whole blood rather than plasma as the matrix for therapeutic monitoring of FK 506 concentrations.

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Population Pharmacokinetics of Gentamicin and Dosing Optimization for Infants

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.03464-14 ◽

2014 ◽

Vol 59 (1) ◽

pp. 482-489 ◽

Cited By ~ 13

Author(s):

Susanna E. Medellín-Garibay ◽

Aída Rueda-Naharro ◽

Silvia Peña-Cabia ◽

Benito García ◽

Silvia Romano-Moreno ◽

...

Keyword(s):

Body Weight ◽

Therapeutic Drug Monitoring ◽

Population Pharmacokinetics ◽

Drug Monitoring ◽

Pediatric Population ◽

External Validation ◽

Therapeutic Monitoring ◽

Therapeutic Drug ◽

Time Data ◽

Age Related

ABSTRACTThe aim of this study was to characterize and validate the population pharmacokinetics of gentamicin in infants and to determine the influences of clinically relevant covariates to explain the inter- and intraindividual variabilities associated with this drug. Infants receiving intravenous gentamicin and with routine therapeutic drug monitoring were consecutively enrolled in the study. Plasma concentration and time data were retrospectively collected from 208 infants (1 to 24 months old) of the Hospital Universitario Severo Ochoa (Spain), of whom 44% were males (mean age [± standard deviation], 5.8 ± 4.8 months; mean body weight, 6.4 ± 2.2 kg). Data analysis was performed with NONMEM 7.2. One- and two-compartment open models were analyzed to estimate the gentamicin population parameters and the influences of several covariates. External validation was carried out in another population of 55 infants. The behavior of gentamicin in infants exhibits two-compartment pharmacokinetics, with total body weight being the covariate that mainly influences central volume (Vc) and clearance (CL); this parameter was also related to creatinine clearance. Both parameters are age related and different from those reported for neonatal populations. On the basis of clinical presentation and diagnosis, a once-daily dosage regimen of 7 mg/kg of body weight every 24 h is proposed for intravenous gentamicin, followed by therapeutic drug monitoring in order to avoid toxicity and ensure efficacy with minimal blood sampling. Gentamicin pharmacokinetics and disposition were accurately characterized in this pediatric population (infants), with the parameters obtained being different from those reported for neonates and children. These differences should be considered in the dosing and therapeutic monitoring of this antibiotic.

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Probability Assessment Approach to Therapeutic Drug Monitoring: Tobramycin

DICP ◽

10.1177/106002808902300311 ◽

1989 ◽

Vol 23 (3) ◽

pp. 240-244 ◽

Cited By ~ 1

Author(s):

Richard L. Slaughter

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Cost Benefit ◽

Therapeutic Monitoring ◽

Therapeutic Drug ◽

Probability Assessment ◽

Serum Concentrations ◽

Specific Patient ◽

Assessment Approach ◽

Toxic Concentrations

Pharmacokinetic monitoring is an important therapeutic goal of aminoglycoside therapy. The overall goal of this study was to identify specific patient groups that would derive the maximum benefit from therapeutic drug monitoring services. These groups are patient populations with high probabilities of achieving toxic or subtherapeutic concentrations. Out of a total population of 86 stable, noncritically ill patients, 27 toxic concentrations (trough >2.0 μg/mL) occurred in 15 patients. In comparison to patients (n = 46) with therapeutic concentrations (trough < 2.0 μg/mL, peak >4.0 μg/mL), these patients were older (64 ± 11 vs. 54 ± 18years; p < 0.02) and had a higher percentage of females (66.7 vs. 37 percent; p < 0.05). Those patients with subtherapeutic concentrations (43 concentrations in 25 patients) had higher estimated creatinine clearance values than those with therapeutic concentrations (94 ± 45 vs. 74 ± 27 mL/min; p < 0.005). Probability assessment analysis of the data showed a sevenfold increase in toxic concentrations in patients above 50 years. Females over age 50 had 2.3 times the risk of developing toxic concentrations as males over age 50. In contrast, the development of low concentrations was not predicted by age or sex. Underdosage by ≥30 percent was a reasonable predictor (75 percent) of low peak concentrations. Furthermore, toxic concentrations did not occur in patients who were underdosed, justifying dosage increases prior to obtaining serum concentrations in these patients. The group with the highest probability of attaining therapeutic concentrations was males receiving therapeutic doses who were under age 50 (85.5 percent). Therefore, routine measurement of serum concentrations in this group would have limited cost-benefit potential. It is concluded that a probability assessment approach can be used to facilitate the therapeutic monitoring of tobramycin.

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Therapeutic drug monitoring of tricyclic antidepressants.

Clinical Chemistry ◽

10.1093/clinchem/34.5.822 ◽

1988 ◽

Vol 34 (5) ◽

pp. 822-828 ◽

Cited By ~ 51

Author(s):

S H Preskorn ◽

R C Dorey ◽

G S Jerkovich

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Tricyclic Antidepressants ◽

Cost Benefit Analysis ◽

Cost Benefit ◽

Therapeutic Monitoring ◽

Therapeutic Drug ◽

Central Nervous System Toxicity ◽

Day Range ◽

Response Method

Abstract The traditional dose-response method of medication adjustment depends on several assumptions that are not met in the case of tricyclic antidepressants (TCAs), which makes therapeutic drug monitoring (TDM) particularly useful with these drugs. TDM can facilitate treatment by providing objective guidelines for dose adjustment. It provides a means of assessing compliance, ensuring an effective concentration, and avoiding toxicity. The latter is an often-overlooked benefit of therapeutic monitoring of TCAs and yet is just as important as improving response. The cardiac and central nervous system toxicity of TCAs is concentration-dependent and potentially life-threatening. Such toxicity will predictably occur in up to 5% of patients on standard antidepressant doses of TCAs when TDM is not used to rationally adjust the dose. Without TDM, such toxicity is difficult to detect early. A cost/benefit analysis supports the cost effectiveness of TDM as a standard part of TCA chemotherapy when doses in the 100-300 ng/day range are used.

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Influence of Infusion Methods on Therapeutic Drug Monitoring in Pediatric Patients

Drug Intelligence & Clinical Pharmacy ◽

10.1177/106002808602000506 ◽

1986 ◽

Vol 20 (5) ◽

pp. 367-369 ◽

Cited By ~ 9

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.

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Cefiderocol in Critically Ill Patients with Multi-Drug Resistant Pathogens: Real-Life Data on Pharmacokinetics and Microbiological Surveillance

Antibiotics ◽

10.3390/antibiotics10060649 ◽

2021 ◽

Vol 10 (6) ◽

pp. 649

Author(s):

Christina König ◽

Anna Both ◽

Holger Rohde ◽

Stefan Kluge ◽

Otto R. Frey ◽

...

Keyword(s):

Renal Replacement Therapy ◽

Therapeutic Drug Monitoring ◽

Continuous Renal Replacement Therapy ◽

Replacement Therapy ◽

Critically Ill ◽

Drug Monitoring ◽

Critically Ill Patients ◽

Therapeutic Drug ◽

Renal Elimination ◽

Drug Resistant

Cefiderocol is a new siderophore-cephalosporin for the treatment of multi-drug resistant Gram-negative pathogens. As a reserve agent, it will and should be used primarily in critically ill patients in the upcoming years. Due to the novelty of the substance little data on the pharmacokinetics in critically ill patients with septic shock and renal failure (including continuous renal replacement therapy and cytokine adsorber therapy) is available. We performed therapeutic drug monitoring in a cohort of five patients treated with cefiderocol, to improve the knowledge on pharmacokinetics in this vulnerable patient population. As expected for a cephalosporin with predominantly renal elimination the maintenance dose could be reduced in patients with renal impairment or on continuous renal replacement therapy. The manufacturer’s dosing instructions were sufficient to achieve a drug level well above the MIC. However, the addition of a cytokine adsorber might reduce serum levels substantially, so that in this context therapeutic drug monitoring and dose adjustment are recommended.

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