Probability Assessment Approach to Therapeutic Drug Monitoring: Tobramycin

DICP ◽  
1989 ◽  
Vol 23 (3) ◽  
pp. 240-244 ◽  
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.

Therapeutic drug monitoring of tricyclic antidepressants.

1988 ◽  
Vol 34 (5) ◽  
pp. 822-828 ◽  
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.

Therapeutic Drug Monitoring: Psychotropic Drugs

1989 ◽  
Vol 2 (6) ◽  
pp. 403-415 ◽  
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.

Is There a Role for Therapeutic Drug Monitoring of Anti-TNF Monoclonal Antibodies in Inflammatory Bowel Disease

2015 ◽  
Vol 33 (Suppl. 1) ◽  
pp. 70-77 ◽  
Author(s):  
Filip Baert
Keyword(s):  
Monoclonal Antibodies ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Treatment Guidelines ◽  
Therapeutic Drug ◽  
Serum Concentrations ◽  
Short Term ◽  
Clear Dose Response ◽  
Inflammatory Bowel

In recent years it has become clear that therapeutic drug monitoring can be an important tool to optimize outcome and costs of anti TNF treatment including the subcutaneous and fully human monoclonal antibodies. There is a clear dose response curve between early serum concentrations of all monoclonal antibodies and response both short term and long term. The wide variations in early serum concentrations are insufficiently explained by classic pharmacokinetic factors. Low early concentrations can lead to anti-drug antibody formation and ensuing loss of response. Therapeutic drug monitoring allows to rationalize the current practice of dose optimization and the use of concomitant immunomodulator treatment. However more prospective studies are needed before strong recommendations can enter treatment guidelines.

scholarly journals Antibiotic therapeutic drug monitoring in intensive care patients treated with different modalities of extracorporeal membrane oxygenation (ECMO) and renal replacement therapy: a prospective, observational single-center study

Critical Care ◽  
2020 ◽  
Vol 24 (1) ◽  
Author(s):  
Dennis Kühn ◽  
Carlos Metz ◽  
Frederik Seiler ◽  
Holger Wehrfritz ◽  
Sophie Roth ◽  
...  
Keyword(s):  
Intensive Care ◽  
Renal Replacement Therapy ◽  
Therapeutic Drug Monitoring ◽  
Extracorporeal Membrane Oxygenation ◽  
Replacement Therapy ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Serum Concentrations ◽  
Icu Patients ◽  
Intensive Care Patients

Abstract Background Effective antimicrobial treatment is key to reduce mortality associated with bacterial sepsis in patients on intensive care units (ICUs). Dose adjustments are often necessary to account for pathophysiological changes or renal replacement therapy. Extracorporeal membrane oxygenation (ECMO) is increasingly being used for the treatment of respiratory and/or cardiac failure. However, it remains unclear whether dose adjustments are necessary to avoid subtherapeutic drug levels in septic patients on ECMO support. Here, we aimed to evaluate and comparatively assess serum concentrations of continuously applied antibiotics in intensive care patients being treated with and without ECMO. Methods Between October 2018 and December 2019, we prospectively enrolled patients on a pneumological ICU in southwest Germany who received antibiotic treatment with piperacillin/tazobactam, ceftazidime, meropenem, or linezolid. All antibiotics were applied using continuous infusion, and therapeutic drug monitoring of serum concentrations (expressed as mg/L) was carried out using high-performance liquid chromatography. Target concentrations were defined as fourfold above the minimal inhibitory concentration (MIC) of susceptible bacterial isolates, according to EUCAST breakpoints. Results The final cohort comprised 105 ICU patients, of whom 30 were treated with ECMO. ECMO patients were significantly younger (mean age: 47.7 vs. 61.2 years; p < 0.001), required renal replacement therapy more frequently (53.3% vs. 32.0%; p = 0.048) and had an elevated ICU mortality (60.0% vs. 22.7%; p < 0.001). Data on antibiotic serum concentrations derived from 112 measurements among ECMO and 186 measurements from non-ECMO patients showed significantly lower median serum concentrations for piperacillin (32.3 vs. 52.9; p = 0.029) and standard-dose meropenem (15.0 vs. 17.8; p = 0.020) in the ECMO group. We found high rates of insufficient antibiotic serum concentrations below the pre-specified MIC target among ECMO patients (piperacillin: 48% vs. 13% in non-ECMO; linezolid: 35% vs. 15% in non-ECMO), whereas no such difference was observed for ceftazidime and meropenem. Conclusions ECMO treatment was associated with significantly reduced serum concentrations of specific antibiotics. Future studies are needed to assess the pharmacokinetic characteristics of antibiotics in ICU patients on ECMO support.

scholarly journals Evidence-based Implementation of Free Phenytoin Therapeutic Drug Monitoring

2000 ◽  
Vol 46 (8) ◽  
pp. 1132-1135 ◽  
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 &lt;8% or &gt;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.

scholarly journals A Moving Target—Vancomycin Therapeutic Monitoring

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.

scholarly journals 1538. Who Will Benefit From Therapeutic Drug Monitoring of Ganciclovir?

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S560-S561
Author(s):  
Anne-Grete Martson ◽  
Marieke G G Sturkenboom ◽  
Stefan P Berger ◽  
Kevin Damman ◽  
Erik A M Verschuuren ◽  
...  
Keyword(s):  
Renal Function ◽  
Therapeutic Drug Monitoring ◽  
Observational Study ◽  
Drug Monitoring ◽  
Drug Formulation ◽  
Therapeutic Window ◽  
Therapeutic Drug ◽  
Solid Organ ◽  
Cell Transplant ◽  
Specific Patient

Abstract Background Oral valganciclovir and intravenous ganciclovir are used for prophylaxis, treatment, and pre-emptive treatment of cytomegalovirus and human herpesvirus 6. It is important to estimate the exposure to these antivirals, as deviating levels can cause adverse events or induce acquired drug resistance, which can both lead to treatment failure. Therapeutic drug monitoring (TDM) is a good tool to estimate drug exposure in these patients. With this observational study we aimed to evaluate which patients would benefit most from TDM. Methods An observational study was performed in adult solid-organ and stem cell transplant recipients on routine (val)ganciclovir (dosed according to renal function, weight and indication). As valganciclovir is a prodrug of ganciclovir, only the latter was measured. Ganciclovir trough (Ctrough) and peak (Cpeak) concentrations were measured with a validated LC-MS/MS assay. The target concentrations defined for the study were 1–2 mg/L and 2–4 mg/L for prophylaxis and treatment, respectively, and over 5 mg/L toxic. Results From June 2018 to April 2019, 66 patients were included. Within this timeframe, 236 Ctrough and 52 Cpeak were measured with median of 4 samples per patient. The median Ctrough was 1.1 mg/L and 2.3 mg/L for prophylaxis and treatment, respectively. Over 50% of the concentrations were out of the therapeutic window. The median creatinine for all measurements was 100 µmol/L. Observational analysis showed patients with kidney failure and on continuous renal replacement therapy (CVVH) had more concentrations measured out of the predefined range (Figures 1 and 2). For one individual with augmented renal clearance we observed significantly lower concentrations during routine dosing. 6 toxic concentrations were measured (5 subjects); creatinine concentrations ranged 71–527 µmol/L in these individuals. A preliminary linear-mixed model analysis did not show drug formulation, age or gender as a significant predictor for ganciclovir concentrations. Conclusion We believe that patients with decreased renal function, on CVVH or showing changes in renal function might benefit from TDM to guide therapy. TDM of ganciclovir for patients without renal failure remains debatable. Further studies with specific patient groups are needed to confirm these results. Disclosures All authors: No reported disclosures.

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

1994 ◽  
Vol 40 (12) ◽  
pp. 2247-2253 ◽  
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.

scholarly journals Population Pharmacokinetics of Gentamicin and Dosing Optimization for Infants

2014 ◽  
Vol 59 (1) ◽  
pp. 482-489 ◽  
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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