Individualized Vancomycin Dosing with Therapeutic Drug Monitoring and Pharmacokinetic Consultation Service: A Large-Scale Retrospective Observational Study

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.

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Large-Scale Variability of Inpatient Tacrolimus Therapeutic Drug Monitoring at an Academic Transplant Center

Therapeutic Drug Monitoring ◽

10.1097/ftd.0000000000000526 ◽

2018 ◽

Vol 40 (4) ◽

pp. 394-400 ◽

Cited By ~ 4

Author(s):

Garth W. Strohbehn ◽

Warren W. Pan ◽

Christopher M. Petrilli ◽

Lauren Heidemann ◽

Sophia Larson ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Large Scale ◽

Therapeutic Drug ◽

Transplant Center

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A Prospective Multicenter Clinical Observational Study on Vancomycin Efficiency and Safety With Therapeutic Drug Monitoring

Clinical Infectious Diseases ◽

10.1093/cid/ciy680 ◽

2018 ◽

Vol 67 (suppl_2) ◽

pp. S249-S255 ◽

Cited By ~ 10

Author(s):

Xiaoyu Liang ◽

Yaxing Fan ◽

Minjie Yang ◽

Jing Zhang ◽

Jufang Wu ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Observational Study ◽

Drug Monitoring ◽

Therapeutic Drug

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Therapeutic drug monitoring of second-generation antipsychotics in pediatric patients: an observational study in real-life settings

European Journal of Clinical Pharmacology ◽

10.1007/s00228-015-1982-0 ◽

2015 ◽

Vol 72 (3) ◽

pp. 285-293 ◽

Cited By ~ 13

Author(s):

Marco Pozzi ◽

Dario Cattaneo ◽

Sara Baldelli ◽

Serena Fucile ◽

Annalisa Capuano ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Observational Study ◽

Drug Monitoring ◽

Second Generation ◽

Pediatric Patients ◽

Real Life ◽

Therapeutic Drug ◽

Second Generation Antipsychotics

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Revisiting the role of therapeutic drug monitoring in optimizing treatment outcomes in patients of bipolar affective disorders receiving lithium therapy: a prospective observational study

International Journal of Advances in Medicine ◽

10.18203/2349-3933.ijam20203064 ◽

2020 ◽

Vol 7 (8) ◽

pp. 1237

Author(s):

Santanu Munshi ◽

Agnik Pal

Keyword(s):

Therapeutic Drug Monitoring ◽

Observational Study ◽

Drug Monitoring ◽

Affective Disorders ◽

Bipolar Affective Disorder ◽

Tertiary Care ◽

Lithium Therapy ◽

Therapeutic Drug ◽

Team Approach ◽

Bipolar Affective Disorders

Background: Lithium continues to be considered first-line therapy for treatment of acute mania, acute mixed bipolar disease and long-term prophylaxis of bipolar disorder. Present study was done to study the pattern of drug therapy in bipolar affective disorder patients with special reference to lithium in the routine psychiatric outpatients care setting of a tertiary care teaching hospital as well as to understand the prospect of therapeutic drug monitoring in optimization of lithium therapy based on outcome.Methods: It was a prospective, non-randomized, observational study of a cohort of subjects who are suffering from bipolar affective disorders and on lithium therapy. Patients were prospectively followed up three monthly for three visits with therapeutic drug monitoring of their plasma lithium level, as and when advised by the treating physician, and pre-formed questionnaires.Results: Results revealed there was significant improvement in symptoms of patients who were monitored with therapeutic drug monitoring and prescribed lithium therapy in accordance with clinical pharmacological consultation for optimal dosing resulting in optimal benefit to patients.Conclusions: With regular therapeutic monitoring, optimal target serum lithium levels can be achieved with dosage modifications thereby reducing the risk of toxicity with improved drug compliance. Thus, individualization of dosing and optimization of treatment can be achieved by dependable analytical laboratory services, better psycho-education, family support and overall a disease-based management team approach with the involvement of clinical Pharmacologist to meet the complexities of lithium therapy.

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Levetiracetam Therapeutic Drug Monitoring in a Large Cohort of Korean Epileptic Patients

Pharmaceuticals ◽

10.3390/ph14080826 ◽

2021 ◽

Vol 14 (8) ◽

pp. 826

Author(s):

Changhee Ha ◽

Hyun-Seung Lee ◽

Eun Yeon Joo ◽

Young-Min Shon ◽

Seung Bong Hong ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Large Scale ◽

Therapeutic Drug ◽

Chromatography Tandem Mass Spectrometry ◽

Generalized Seizures ◽

Epileptic Patients ◽

Serum Trough ◽

Liquid Chromatography Tandem Mass ◽

Patient Noncompliance

Levetiracetam is a new antiepileptic drug (AED) used for treating and preventing partial or generalized seizures. The usefulness of levetiracetam therapeutic drug monitoring (TDM) is related to inter- or intra-individual pharmacokinetic variability, drug interactions, and patient noncompliance. We aimed to investigate the levetiracetam TDM status in Korean epilepsy patients. Serum trough levetiracetam concentrations were measured using liquid chromatography–tandem mass spectrometry in 710 samples from 550 patients. The median (range) daily and weight-adjusted levetiracetam doses were 1500 (20–5000) mg and 25.5 (3.03–133.0) mg/kg, respectively. Patients on levetiracetam monotherapy constituted only 19.5% of the population, while 30.1% were on co-medication with valproate and 56.0% with enzyme-inducing AEDs (EIAEDs). Observed levetiracetam concentrations were widely distributed, ranging 0.8–95 mg/L, with a median of 17.3 mg/L. Levetiracetam concentrations were therapeutic, supra-therapeutic, and sub-therapeutic in 58.5% (n = 393), 11.6% (n = 78), and 29.9% (n = 201) of samples, respectively. There was a strong correlation between weight-adjusted levetiracetam dosage and concentrations (ρ = 0.6896, p < 0.0001). In this large-scale clinical study, a large inter-individual difference in levetiracetam pharmacokinetics was observed, and levetiracetam concentrations were influenced by EIAEDs. For individual dose adjustments and monitoring compliance, routine levetiracetam TDM is needed in epilepsy patients.

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