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

2006 ◽  
Vol 40 (1) ◽  
pp. 143-146 ◽  
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

scholarly journals Pharmacokinetics of enalapril in patients with arterial hypertension depending on the glomerular filtration rate

2019 ◽  
Vol 10 (3) ◽  
pp. 37-41
Author(s):  
Marina V. Zhuravleva ◽  
Aleksei B. Prokofiev ◽  
Artem I. Dmitriev ◽  
Sergei A. Belkov ◽  
Evgenii S. Melnikov ◽  
...  
Keyword(s):  
Renal Function ◽  
Therapeutic Drug Monitoring ◽  
Arterial Hypertension ◽  
Drug Monitoring ◽  
Impaired Renal Function ◽  
Therapeutic Drug ◽  
Main Metabolite ◽  
High Prevalence ◽  
High Doses ◽  
Enalapril And Enalaprilat

Aim. To study the pharmacokinetics of enalapril in patients with arterial hypertension, depending on the value of the prescribed dose of enalapril and the state of renal function to improve the efficiency and safety of treatment. Materials and methods. The study was performed in a group of 328 patients (107 men and 221 women aged 43 to 88 years) who received treatment for hypertension of 1-2 degrees. As the main antihypertensive drug was prescribed enalapril in doses of 2.5 to 20 mg twice a day. Patients underwent therapeutic drug monitoring to determine the concentration of enalapril and its metabolite - enalaprilat. Results. Among the examined patients in 31% of cases there was a decrease in GFR less than 60 ml/min, and in 9 (3%) patients GFR was less than 30 ml/min. This indicates a high prevalence of chronic kidney disease among patients with hypertension. During therapeutic drug monitoring enalapril in patients with hypertension and reduced GFR (less than 60 ml/min) serum concentration of the main metabolite was 1.5-2 times higher than in patients with GFR more than 60 ml/min. Conclusion. It is advisable to carry out therapeutic drug monitoring to determine the concentrations of enalapril and enalaprilat in the serum of patients receiving the drug in high doses and having impaired renal function. In the appointment of enalapril in high doses to patients with reduced GFR, the concentration of enalaprilat significantly exceeds similar indicators in patients with normal GFR and in some cases goes beyond the therapeutic range, indicating the need to consider the correction of the treatment regimen.

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.

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

Antibiotics ◽  
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.

scholarly journals Use of Therapeutic Drug Monitoring to Characterize Cefepime-Induced Neurotoxicity

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.

scholarly journals Extensive Therapeutic Drug Monitoring of Colistin in Critically Ill Patients Reveals Undetected Risks

2020 ◽  
Vol 8 (3) ◽  
pp. 415 ◽  
Author(s):  
Stefan Felix Ehrentraut ◽  
Stefan Muenster ◽  
Stefan Kreyer ◽  
Nils Ulrich Theuerkauf ◽  
Christian Bode ◽  
...  
Keyword(s):  
Renal Function ◽  
Therapeutic Drug Monitoring ◽  
Critically Ill ◽  
Drug Monitoring ◽  
Critically Ill Patients ◽  
Plasma Levels ◽  
Therapeutic Drug ◽  
The Right ◽  
The Impact ◽  
Current Guidelines

(1) Background: With the rise of multi-/pan-drug resistant (MDR/PDR) pathogens, the less utilized antibiotic Colistin has made a comeback. Colistin fell out of favor due to its small therapeutic range and high potential for toxicity. Today, it is used again as a last resort substance in treating MDR/PDR pathogens. Although new guidelines with detailed recommendations for Colistin dosing are available, finding the right dose in critically ill patients with renal failure remains difficult. Here, we evaluate the efficiency of the current guidelines’ recommendations by using high resolution therapeutic drug monitoring of Colistin. (2) Methods: We analyzed plasma levels of Colistin and its prodrug colisthimethate sodium (CMS) in 779 samples, drawn from eight PDR-infected ICU patients, using a HPLC-MS/MS approach. The impact of renal function on proper Colistin target levels was assessed. (3) Results: CMS levels did not correlate with Colistin levels. Over-/Underdosing occurred regardless of renal function and mode of renal replacement therapy. Colistin elimination half-time appeared to be longer than previously reported. (4) Conclusion: Following dose recommendations from the most current guidelines does not necessarily lead to adequate Colistin plasma levels. Use of Colistin without therapeutic drug monitoring might be unsafe and guideline adherence does not warrant efficient target levels in critically ill patients.

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

2017 ◽  
Vol 61 (6) ◽  
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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