P-012 YI Decisions to Dose Optimize Infliximab Using Pre-adjustment Therapeutic Drug Monitoring Result in Higher Trough Concentrations and Improved Endoscopic Outcomes

ABSTRACT Voriconazole is a broad-spectrum triazole antifungal and the first-line treatment for invasive aspergillosis (IA). The aim of this research was to study the dose adjustments of voriconazole as well as the affecting factors influencing voriconazole trough concentrations in Asian children to optimize its daily administration. Clinical data were analyzed of inpatients 2 to 14 years old who were subjected to voriconazole trough concentration monitoring from 1 June 2015 to 1 December 2017. A total of 138 voriconazole trough concentrations from 42 pediatric patients were included. Voriconazole trough concentrations at steady state ranged from 0.02 to 9.35 mg/liter, with high inter- and intraindividual variability. Only 50.0% of children achieved the target range (1.0 to 5.5 mg/liter) at initial dosing, while 35.7% of children were subtherapeutic, and 14.3% of children were supratherapeutic at initial dosing. There was no correlation between initial trough concentrations and initial dosing. A total of 28.6% of children (12/42) received an adjusted dose according to trough concentrations. Children <6, 6 to 12, and >12 years old required a median oral maintenance dose to achieve the target range of 11.1, 7.2, and 5.3 mg/kg twice daily, respectively (P = 0.043). The average doses required to achieved the target range were 7.7 mg/kg and 5.6 mg/kg, respectively, and were lower than the recommended dosage (P = 0.033 and 0.003, respectively). Affecting factors such as administration routes and coadministration with proton pump inhibitors (PPIs) explained 55.3% of the variability in voriconazole exposure. Therapeutic drug monitoring (TDM) of voriconazole could help to individualize antifungal therapy for children and provide guidelines for TDM and dosing optimization in Asian children.

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Use of Therapeutic Drug Monitoring to Characterize Cefepime-Induced Neurotoxicity

10.1101/2020.08.13.250456 ◽

2020 ◽

Author(s):

Veena Venugopalan ◽

Cara Nys ◽

Natalie Hurst ◽

Yiqing Chen ◽

Maria Bruzzone ◽

...

Keyword(s):

Renal Function ◽

Therapeutic Drug Monitoring ◽

Trough Concentration ◽

Drug Monitoring ◽

Hospitalized Patients ◽

Therapeutic Drug ◽

Eeg Abnormalities ◽

Increased Risk ◽

Trough Concentrations ◽

The Relationship

AbstractBackgroundThe incidence of cefepime-induced neurotoxicity (CIN) in hospitalized patients is highly variable. Although greater cefepime exposures incite neurotoxicity, data evaluating trough thresholds associated with CIN remains limited. The objectives of this study were to evaluate the incidence of CIN, assess the relationship between cefepime trough concentrations and CIN, investigate clinical factors associated with CIN, and describe electroencephalogram (EEG) abnormalities in CIN.MethodsThis was a retrospective study of adult patients who had received ≥ 5 days of cefepime with ≥ 1 trough concentration > 25 mg/L. Potential CIN cases were identified utilizing neurological symptoms, neurologist assessments, EEG findings and improvement of neurotoxicity after cefepime discontinuation.ResultsOne-hundred and forty-two patients were included. The incidence of CIN was 13% (18/142). The mean cefepime trough concentration in CIN patients was significantly greater than the non-neurotoxicity group (74.2 mg/L ± 41.1 vs. 46.6 mg/L ± 23, p=0.015). Lower renal function (creatinine clearance < 30 ml/min), greater time to therapeutic drug monitoring (TDM) (≥72 hours), and each 1 mg/mL rise in cefepime trough were independently associated with increased risk of CIN. Moderate generalized slowing of the background rhythm was the most common EEG pattern associated with CIN.ConclusionCefepime should be used cautiously in hospitalized patients due to the risk of neurotoxicity. Patients with greater renal function and those who had early cefepime TDM (≤ 72 hours) had lower risk of CIN.

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Assessing the Impact of Substance use and Hepatitis Coinfection on Atazanavir and Lopinavir Trough Concentrations in HIV-Infected Patients During Therapeutic Drug Monitoring

Therapeutic Drug Monitoring ◽

10.1097/ftd.0b013e31806db8ae ◽

2007 ◽

Vol 29 (5) ◽

pp. 560-565 ◽

Cited By ~ 10

Author(s):

Judianne Slish ◽

Qing Ma ◽

Barry S Zingman ◽

Richard C Reichman ◽

Margaret A Fischl ◽

...

Keyword(s):

Substance Use ◽

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Therapeutic Drug ◽

Trough Concentrations ◽

The Impact

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Therapeutic drug monitoring of once daily tobramycin in cystic fibrosis—caution with trough concentrations

Journal of Cystic Fibrosis ◽

10.1016/j.jcf.2006.05.015 ◽

2007 ◽

Vol 6 (2) ◽

pp. 125-130 ◽

Cited By ~ 23

Author(s):

Kingsley P. Coulthard ◽

Daniel G. Peckham ◽

Steven P. Conway ◽

Carol A. Smith ◽

Jan Bell ◽

...

Keyword(s):

Cystic Fibrosis ◽

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Therapeutic Drug ◽

Once Daily ◽

Trough Concentrations

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Optimizing Outcomes Using Vancomycin Therapeutic Drug Monitoring in Patients with MRSA Bacteremia: Trough Concentrations or Area Under the Curve?

Diagnostic Microbiology and Infectious Disease ◽

10.1016/j.diagmicrobio.2021.115442 ◽

2021 ◽

pp. 115442

Author(s):

Madeline M. Johnston ◽

Vanthida Huang ◽

Scott T. Hall ◽

Mitchell S. Buckley ◽

Dale Bikin ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Area Under The Curve ◽

Therapeutic Drug ◽

Trough Concentrations

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Inappropriate Vancomycin Therapeutic Drug Monitoring in Hospitalized Pediatric Patients Increases Pediatric Trauma and Hospital Costs

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-17.2.159 ◽

2012 ◽

Vol 17 (2) ◽

pp. 159-165 ◽

Cited By ~ 2

Author(s):

Manika Suryadevara ◽

Kelly E. Steidl ◽

Luke A. Probst ◽

Jana Shaw

Keyword(s):

Health Care ◽

Therapeutic Drug Monitoring ◽

Health Care Provider ◽

Care Provider ◽

Drug Monitoring ◽

Hospital Cost ◽

Pediatric Patients ◽

Tertiary Care ◽

Therapeutic Drug ◽

Trough Concentrations

OBJECTIVES The objective of this study was to measure the appropriateness of vancomycin monitoring in a pediatric tertiary care center and to evaluate the effectiveness of two interventions, autonomous pharmacy therapeutic drug monitoring and health care provider education, in reducing avoidable pediatric patient trauma and hospital cost. METHODS A retrospective chart review evaluating vancomycin therapeutic drug monitoring (TDM) in pediatric inpatients was performed before and after the introduction of an autonomous pharmacy TDM program and health care provider (HCP) education. RESULTS Thirty-five patients were included in our study, prior to any intervention. Of these, 9% of patients had trough concentrations appropriately deferred. Of the total of 64 trough concentrations obtained, 94% were considered to be inappropriate. After the start of the autonomous pharmacy TDM program, of the 54 eligible patients (111 troughs), 9% had trough concentrations appropriately deferred, and 34% were inappropriate. In the 3-month period following the introduction of HCP education in combination with pharmacy TDM, we identified 27 eligible patients. Among those, 15% of the patients had trough concentrations appropriately deferred. Of the 43 trough concentrations obtained, only 9% were considered to be inappropriate. The combination of pharmacy TDM with HCP education decreased annualized hospital cost by 60%, from $13,080 to $5232. CONCLUSIONS Inappropriate vancomycin TDM occurs commonly in our institution, resulting in unnecessary hospital cost and patient trauma. The combination of pharmacy TDM and HCP education significantly improved clinical practice; however, results were short-lived. Further interventions, such as computer based order entry, will likely be needed to reinforce and improve long-term TDM practice in pediatric patients.

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Variability in Trough Total and Unbound Teicoplanin Concentrations and Achievement of Therapeutic Drug Monitoring Targets in Adult Patients with Hematological Malignancy

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02466-16 ◽

2017 ◽

Vol 61 (6) ◽

Cited By ~ 10

Author(s):

Catherine J. Byrne ◽

Jason A. Roberts ◽

Brett McWhinney ◽

Jerome P. Fennell ◽

Philomena O'Byrne ◽

...

Keyword(s):

Renal Function ◽

Body Weight ◽

Therapeutic Drug Monitoring ◽

Creatinine Clearance ◽

Trough Concentration ◽

Drug Monitoring ◽

Hematological Malignancy ◽

Therapeutic Drug ◽

Factors Associated ◽

Trough Concentrations

ABSTRACT The objective of this study was to explore the following aspects of teicoplanin use in patients with hematological malignancy: early attainment of target trough concentrations with current high-dose teicoplanin regimens, variability in unbound teicoplanin fractions, factors associated with observed total and unbound trough concentrations, efficacy and toxicity, and renal function estimation. This was a single-center, prospective study. Samples for determination of trough concentrations were taken on days 3, 4, 7, and 10. Total and unbound teicoplanin concentrations were determined using validated high-performance liquid chromatography methods. Regression analyses were used to identify the factors associated with the trough concentration. Thirty teicoplanin-treated adults with hematological malignancy were recruited. Despite the use of dosages higher than the conventional dosages, the proportions of patients with a trough concentration of ≥20 mg/liter at 48 h and at 72 h were 16.7% and 37.9%, respectively. Renal function was significantly negatively associated with total trough concentrations at 48 h and 72 h (P < 0.05). For an average hematological malignancy patient (creatinine clearance = 70 ml/min), sequential loading doses of at least 12 mg/kg of body weight may be needed to achieve early adequate exposure. In the absence of measured creatinine clearance, estimates obtained using the Cockcroft-Gault (total body weight) equation could prove to be an acceptable surrogate. The unbound fractions of teicoplanin were highly variable (3.4 to 18.8%). Higher unbound fractions were observed in patients with low serum albumin concentrations. Teicoplanin was well tolerated. Teicoplanin loading doses higher than those in current use appear to be necessary. Increased dosing is needed in patients with increased renal function. The high variability in protein binding supports the contention for therapeutic drug monitoring of unbound teicoplanin concentrations. (This study has been registered with EudraCT under registration no. 2013-004535-72.)

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Multicenter Study of Voriconazole Pharmacokinetics and Therapeutic Drug Monitoring

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00626-12 ◽

2012 ◽

Vol 56 (9) ◽

pp. 4793-4799 ◽

Cited By ~ 171

Author(s):

Michael J. Dolton ◽

John E. Ray ◽

Sharon C.-A. Chen ◽

Kingsley Ng ◽

Lisa G. Pont ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Adverse Events ◽

Drug Monitoring ◽

Medical Records ◽

Fungal Infections ◽

Therapeutic Drug ◽

Single Institution ◽

First Line ◽

Trough Concentrations ◽

Small Patient

ABSTRACTVoriconazole is a first-line agent in the treatment of many invasive fungal infections and is known to display highly variable pharmacokinetics. Previous studies of voriconazole therapeutic drug monitoring (TDM) have suggested concentration monitoring to be clinically useful but have been limited by small patient samples at a single institution. This multicenter retrospective study aimed to investigate relationships between voriconazole concentration and clinical outcomes and adverse events and to assess clinical factors and drug interactions that may affect voriconazole concentration. Medical records were reviewed for patients who received voriconazole and had at least 1 concentration measured at seven hospitals in Australia. The study included 201 patients with 783 voriconazole trough concentrations. Voriconazole concentrations of <1.7 mg/liter were associated with a significantly greater incidence of treatment failure (19/74 patients [26%]) than concentrations of ≥1.7 mg/liter (6/89 patients [7%]) (P< 0.01). Neurotoxic adverse events (visual and auditory hallucinations) occurred more frequently at voriconazole concentrations of >5 mg/liter (10/31 patients [32%]) than at concentrations of ≤5 mg/liter (2/170 patients [1.2%]) (P< 0.01). Multiple regression analysis of voriconazole concentration identified associations between increasing patient weight, oral administration of voriconazole, and coadministration of phenytoin or rifampin and significantly reduced concentrations, and associations between increasing patient age and coadministration of proton pump inhibitors and increased concentrations. Coadministration of glucocorticoids was found to significantly reduce voriconazole concentrations, inferring a previously unreported drug interaction between glucocorticoids and voriconazole.

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Therapeutic Drug Monitoring in Buprenorphine/Naloxone Treatment for Opioid Use Disorder: Clinical Feasibility and Optimizing Assay Precision

Pharmacopsychiatry ◽

10.1055/a-1083-6842 ◽

2020 ◽

Vol 53 (03) ◽

pp. 115-121

Author(s):

Hesham Farouk Elarabi ◽

Nael Hasan ◽

John Marsden ◽

Doaa Radwan ◽

Abdu Adem ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Maintenance Treatment ◽

Limit Of Detection ◽

Opioid Use Disorder ◽

Therapeutic Drug ◽

Opioid Use ◽

Limit Of Quantitation ◽

Trough Concentrations ◽

Assay Precision

Abstract Introduction Compliance with sublingual buprenorphine/naloxone (SL-BUP/NX) is associated with higher abstinence from illicit opioid use. Therapeutic drug monitoring (TDM) has been recommended for adherence monitoring of buprenorphine (BUP) maintenance treatment for opioid use disorder (OUD), but to date there have been no reported clinical applications. In this TDM feasibility study, we investigated BUP assay precision in 15 adults with OUD who had been stabilized on buprenorphine/naloxone. Methods Using solid phase extraction, BUP recovery was contrasted at 100 mMol and 1 Molar of acetic acid wash solution. Precision was determined by applying the condition generating highest recovery using 0.2 ng/mL and 10 ng/mL standards. Four blood samples were drawn to examine the BUP peak and trough plasma concentrations, and BUP elimination rate was estimated. BUP recovery was examined again in a random sample and contrasted with the concentration predicted applying first-order kinetics. Results Higher BUP recovery was achieved with 1 Molar wash (94.3%; p=0.05). Precision ranged from 15–20%. The estimated limit of detection (LoD) and limit of quantitation (LoQ) were 0.02 and 0.069 ng/mL, respectively. BUP peak and trough concentrations were successfully examined, and BUP trough concentrations were replicated confirming steady state. BUP concentrations were predicted at a variance of −7.20% to 1.54 %. Conclusions TDM for BUP maintenance treatment of OUD is feasible, and simple adjustment of the assay conditions enhances BUP recovery.

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