PKP-026 Therapeutic drug monitoring of vancomycin and evolution of renal function in patients with first time prosthesis replacement

Therapeutic drug monitoring (TDM) has consistently been shown to be useful for optimization of drug therapy. For the first time, a method has been developed for the text analysis of TDM in SPCs in that a catalogue SPC-ContentTDM (SPCCTDM) provides a codification of the content of TDM in SPCs. It consists of six structure-related items (dose, adverse drug reactions, drug interactions, overdose, pregnancy/breast feeding, and pharmacokinetics) according to implicit or explicit references to TDM in paragraphs of the SPC, and four theory-guided items according to the information about ranges of plasma concentrations and a recommendation of TDM in the SPC. The catalogue is regarded as valid for the text analysis of SPCs with respect to TDM. It can be used in the comparison of SPCs, in the comparison with medico-scientific evidence and for the estimation of the perception of TDM in SPCs by the reader. Regarding the approach as a model of text mining, it may be extended for evaluation of other aspects reported in SPCs.

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SPCCTDM, a Catalogue for Analysis of Therapeutic Drug Monitoring Related Contents in the Drug Prescription Information

International Journal of Knowledge Discovery in Bioinformatics ◽

10.4018/jkdb.2010040101 ◽

2010 ◽

Vol 1 (2) ◽

pp. 1-11

Author(s):

Sven Ulrich ◽

Pierre Baumann ◽

Andreas Conca ◽

Hans-Joachim Kuss ◽

Viktoria Stieffenhofer ◽

...

Keyword(s):

Drug Therapy ◽

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Text Analysis ◽

Scientific Evidence ◽

Drug Prescription ◽

Plasma Concentrations ◽

Therapeutic Drug ◽

Drug Reactions ◽

First Time

Therapeutic drug monitoring (TDM) has consistently been shown to be useful for optimization of drug therapy. For the first time, a method has been developed for the text analysis of TDM in SPCs in that a catalogue SPC-ContentTDM (SPCCTDM) provides a codification of the content of TDM in SPCs. It consists of six structure-related items (dose, adverse drug reactions, drug interactions, overdose, pregnancy/breast feeding, and pharmacokinetics) according to implicit or explicit references to TDM in paragraphs of the SPC, and four theory-guided items according to the information about ranges of plasma concentrations and a recommendation of TDM in the SPC. The catalogue is regarded as valid for the text analysis of SPCs with respect to TDM. It can be used in the comparison of SPCs, in the comparison with medico-scientific evidence and for the estimation of the perception of TDM in SPCs by the reader. Regarding the approach as a model of text mining, it may be extended for evaluation of other aspects reported in SPCs.

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.1402 ◽

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.

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A new population pharmacokinetic model for vancomycin in patients with variable renal function: Therapeutic drug monitoring based on extended covariate model using CKD‐EPI estimation

Journal of Clinical Pharmacy and Therapeutics ◽

10.1111/jcpt.12995 ◽

2019 ◽

Vol 44 (5) ◽

pp. 750-759

Author(s):

Dong‐Jin Kim ◽

Dong‐Hwan Lee ◽

Sangzin Ahn ◽

Jinah Jung ◽

Sungmin Kiem ◽

...

Keyword(s):

Renal Function ◽

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Population Pharmacokinetic Model ◽

Pharmacokinetic Model ◽

Therapeutic Drug ◽

Population Pharmacokinetic ◽

Covariate Model

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Saliva versus Plasma Therapeutic Drug Monitoring of Pregabalin in Jordanian Patients

Drug Research ◽

10.1055/a-0600-2113 ◽

2018 ◽

Vol 68 (10) ◽

pp. 596-600 ◽

Cited By ~ 4

Author(s):

Nasir Idkaidek ◽

Salim Hamadi ◽

Manal El-Assi ◽

Ahmad Al-Shalalfeh ◽

Ahmad Al-Ghazawi

Keyword(s):

Therapeutic Drug Monitoring ◽

Women Elderly ◽

Drug Monitoring ◽

Good Alternative ◽

Therapeutic Drug ◽

P Value ◽

Two Samples ◽

Significant Difference ◽

Class 1 ◽

First Time

AbstractThe objective is using saliva instead of plasma for pregabalin therapeutic drug monitoring (TDM) since saliva reflects the free non–protein bound drug concentration, simple and noninvasive sampling, cheaper and does not require the expertise of drawing blood. Forty four patients participated in this study, two samples of saliva and another two of blood were taken from each patient; first sample of both saliva and blood is the trough sample and was taken just before the first dose of the day and second sample is the peak sample and was taken 1 h after taking the first dose of the day. Descriptive statistics and t-testing after log transformation were done using Excel, p-value=0.05 was adopted for significant difference. Optimized effective intestinal permeability of pregabalin was estimated by PK-Sim program version 7. This study for the first time revealed that pregabalin is excreted in saliva and classified as class 1 based on Salivary Excretion Classification System (SECS). A good correlation of 0.71-0.83 between Cmin and Cmax of plasma and saliva pregabalin was observed respectively which indicate that saliva sampling is a good alternative matrix for pregabalin TDM. C/D-ratios were calculated to demonstrate pharmacokinetic variability of Pregabalin; the results showed that C/D-ratio was higher in women, elderly and in those patients who had Scr.≥0.9 mg/dl. Proposed pregabalin therapeutic ranges are 0.7 to 1.84 µg/ml in plasma and 0.055 to 0.145 µg/ml in saliva, for neuropathic pain, diabetic neuropathy and disc prolapse patients.

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Therapeutic Drug Monitoring of Meropenem and Piperacillin in Critical Illness—Experience and Recommendations from One Year in Routine Clinical Practice

Antibiotics ◽

10.3390/antibiotics9030131 ◽

2020 ◽

Vol 9 (3) ◽

pp. 131

Author(s):

Christina Scharf ◽

Michael Paal ◽

Ines Schroeder ◽

Michael Vogeser ◽

Rika Draenert ◽

...

Keyword(s):

Renal Function ◽

Clinical Practice ◽

Therapeutic Drug Monitoring ◽

Critically Ill ◽

Drug Monitoring ◽

Critically Ill Patients ◽

Therapeutic Drug ◽

Beta Lactam ◽

Target Attainment ◽

Number Of Patients

Various studies have reported insufficient beta-lactam concentrations in critically ill patients. The extent to which therapeutic drug monitoring (TDM) in clinical practice can reduce insufficient antibiotic concentrations is an ongoing matter of investigation. We retrospectively evaluated routine meropenem and piperacillin measurements in critically ill patients who received antibiotics as short infusions in the first year after initiating a beta-lactam TDM program. Total trough concentrations above 8.0 mg/L for meropenem and above 22.5 mg/L for piperacillin were defined as the breakpoints for target attainment. We included 1832 meropenem samples and 636 piperacillin samples. We found that 39.3% of meropenem and 33.6% of piperacillin samples did not reach the target concentrations. We observed a clear correlation between renal function and antibiotic concentration (meropenem, r = 0.53; piperacillin, r = 0.63). Patients with renal replacement therapy or creatinine clearance (CrCl) of <70 mL/min had high rates of target attainment with the standard dosing regimens. There was a low number of patients with a CrCl >100 mL/min that achieved the target concentrations with the maximum recommended dosage. Patients with impaired renal function only required TDM if toxic side effects were noted. In contrast, patients with normal renal function required different dosage regimens and TDM-guided therapy to reach the breakpoints of target attainment.

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Neurotoxicity Related to Valganciclovir in a Child With Impaired Renal Function: Usefulness of Therapeutic Drug Monitoring

Annals of Pharmacotherapy ◽

10.1345/aph.1g214 ◽

2006 ◽

Vol 40 (1) ◽

pp. 143-146 ◽

Cited By ~ 14

Author(s):

Hélène Peyrière ◽

Eric Jeziorsky ◽

Anne Jalabert ◽

Marylène Cociglio ◽

Abdelkader Benketira ◽

...

Keyword(s):

Renal Function ◽

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Impaired Renal Function ◽

Therapeutic Drug

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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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