scholarly journals Multicenter Study of Voriconazole Pharmacokinetics and Therapeutic Drug Monitoring

2012 ◽  
Vol 56 (9) ◽  
pp. 4793-4799 ◽  
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.

scholarly journals Software for Dosage Individualization of Voriconazole for Immunocompromised Patients

2013 ◽  
Vol 57 (4) ◽  
pp. 1888-1894 ◽  
Author(s):  
William W. Hope ◽  
Michael VanGuilder ◽  
J. Peter Donnelly ◽  
Nicole M. A. Blijlevens ◽  
Roger J. M. Brüggemann ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Fungal Infections ◽  
Plasma Concentrations ◽  
Therapeutic Drug ◽  
Cell Transplant ◽  
Multiple Model ◽  
Pharmacokinetic Variability ◽  
Hematopoietic Stem ◽  
Wide Range

ABSTRACTThe efficacy of voriconazole is potentially compromised by considerable pharmacokinetic variability. There are increasing insights into voriconazole concentrations that are safe and effective for treatment of invasive fungal infections. Therapeutic drug monitoring is increasingly advocated. Software to aid in the individualization of dosing would be an extremely useful clinical tool. We developed software to enable the individualization of voriconazole dosing to attain predefined serum concentration targets. The process of individualized voriconazole therapy was based on concepts of Bayesian stochastic adaptive control. Multiple-model dosage design with feedback control was used to calculate dosages that achieved desired concentration targets with maximum precision. The performance of the software program was assessed using the data from 10 recipients of an allogeneic hematopoietic stem cell transplant (HSCT) receiving intravenous (i.v.) voriconazole. The program was able to model the plasma concentrations with a high level of precision, despite the wide range of concentration trajectories and interindividual pharmacokinetic variability. The voriconazole concentrations predicted after the last dosages were largely concordant with those actually measured. Simulations provided an illustration of the way in which the software can be used to adjust dosages of patients falling outside desired concentration targets. This software appears to be an extremely useful tool to further optimize voriconazole therapy and aid in therapeutic drug monitoring. Further prospective studies are now required to define the utility of the controller in daily clinical practice.

scholarly journals A Novel, Rapid, and Low-Volume Assay for Therapeutic Drug Monitoring of Posaconazole and Other Long-Chain Azole-Class Antifungal Drugs

mSphere ◽  
2018 ◽  
Vol 3 (6) ◽  
Author(s):  
Gregory R. Wiedman ◽  
Yanan Zhao ◽  
David S. Perlin
Keyword(s):  
Liquid Chromatography ◽  
Therapeutic Drug Monitoring ◽  
Human Serum ◽  
Drug Monitoring ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Therapeutic Drug ◽  
Serum Samples ◽  
Human Serum Samples ◽  
Long Chain

ABSTRACT Clinicians need a better way to accurately monitor the concentration of antimicrobials in patient samples. In this report, we describe a novel, low-sample-volume method to monitor the azole-class antifungal drug posaconazole, as well as certain other long-chain azole-class antifungal drugs in human serum samples. Posaconazole represents an important target for therapeutic drug monitoring (TDM) due to its widespread use in treating invasive fungal infections and well-recognized variability of pharmacokinetics. The current “gold standard” requires trough and peak monitoring through high-pressure liquid chromatography (HPLC) or liquid chromatography-tandem mass spectroscopy (LC-MS/MS). Other methods include bioassays that use highly susceptible strains of fungi in culture plates or 96-well formats to monitor concentrations. Currently, no method exists that is both highly accurate in detecting free drug concentrations and is also rapid. Herein, we describe a new method using reduced graphene oxide (rGO) and a fluorescently labeled aptamer, which can accurately assess clinically relevant concentrations of posaconazole and other long-chain azole-class drugs in little more than 1 h in a total volume of 100 µl. IMPORTANCE This work describes an effective assay for TDM of long-chain azole-class antifungal drugs that can be used in diluted human serum samples. This assay will provide a quick, cost-effective method for monitoring concentrations of drugs such as posaconazole that exhibit well-documented pharmacokinetic variability. Our rGO-aptamer assay has the potential to improve health care for those struggling to treat fungal infections in rural or resource-limited setting.

Therapeutic Drug Monitoring of Voriconazole in the Management of Invasive Fungal Infections: A Critical Review

2015 ◽  
Vol 54 (12) ◽  
pp. 1223-1235 ◽  
Author(s):  
Hazem Elewa ◽  
Eman El-Mekaty ◽  
Ahmed El-Bardissy ◽  
Mary H. H. Ensom ◽  
Kyle John Wilby
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Critical Review ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Therapeutic Drug

scholarly journals Recent Advances in Therapeutic Drug Monitoring of Voriconazole, Mycophenolic Acid, and Vancomycin: A Literature Review of Pediatric Studies

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 1991
Author(s):  
Matylda Resztak ◽  
Joanna Sobiak ◽  
Andrzej Czyrski
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Mycophenolic Acid ◽  
Drug Monitoring ◽  
Pediatric Patients ◽  
Fungal Infections ◽  
Cord Blood Transplantation ◽  
Active Form ◽  
Therapeutic Drug ◽  
Hematopoietic Stem ◽  
Acute Kidney Disease

The review includes studies dated 2011–2021 presenting the newest information on voriconazole (VCZ), mycophenolic acid (MPA), and vancomycin (VAN) therapeutic drug monitoring (TDM) in children. The need of TDM in pediatric patients has been emphasized by providing the information on the differences in the drugs pharmacokinetics. TDM of VCZ should be mandatory for all pediatric patients with invasive fungal infections (IFIs). Wide inter- and intrapatient variability in VCZ pharmacokinetics cause achieving and maintaining therapeutic concentration during therapy challenging in this population. Demonstrated studies showed, in most cases, VCZ plasma concentrations to be subtherapeutic, despite the updated dosages recommendations. Only repeated TDM can predict drug exposure and individualizing dosing in antifungal therapy in children. In children treated with mycophenolate mofetil (MMF), similarly as in adult patients, the role of TDM for MMF active form, MPA, has not been well established and is undergoing continued debate. Studies on the MPA TDM have been carried out in children after renal transplantation, other organ transplantation such as heart, liver, or intestine, in children after hematopoietic stem cell transplantation or cord blood transplantation, and in children with lupus, nephrotic syndrome, Henoch-Schönlein purpura, and other autoimmune diseases. MPA TDM is based on the area under the concentration–time curve; however, the proposed values differ according to the treatment indication, and other approaches such as pharmacodynamic and pharmacogenetic biomarkers have been proposed. VAN is a bactericidal agent that requires TDM to prevent an acute kidney disease. The particular group of patients is the pediatric one. For this group, the general recommendations of the dosing may not be valid due to the change of the elimination rate and volume of distribution between the subjects. The other factor is the variability among patients that concerns the free fraction of the drug. It may be caused by both the patients’ population and sample preconditioning. Although VCZ, MMF, and VAN have been applied in pediatric patients for many years, there are still few issues to be solve regarding TDM of these drugs to ensure safe and effective treatment. Except for pharmacokinetic approach, pharmacodynamics and pharmacogenetics have been more often proposed for TDM.

scholarly journals Dried Blood Spot Analysis Suitable for Therapeutic Drug Monitoring of Voriconazole, Fluconazole, and Posaconazole

2013 ◽  
Vol 57 (10) ◽  
pp. 4999-5004 ◽  
Author(s):  
Kim C. M. van der Elst ◽  
Lambert F. R. Span ◽  
Kai van Hateren ◽  
Karin M. Vermeulen ◽  
Tjip S. van der Werf ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Sampling Method ◽  
Fungal Infections ◽  
Venous Blood ◽  
Blood Sampling ◽  
Dried Blood Spot ◽  
Therapeutic Drug ◽  
Venous Blood Sampling ◽  
Blood Spot

ABSTRACTInvasive aspergillosis and candidemia are important causes of morbidity and mortality in immunocompromised and critically ill patients. The triazoles voriconazole, fluconazole, and posaconazole are widely used for the treatment and prophylaxis of these fungal infections. Due to the variability of the pharmacokinetics of the triazoles among and within individual patients, therapeutic drug monitoring is important for optimizing the efficacy and safety of antifungal treatment. A dried blood spot (DBS) analysis was developed and was clinically validated for voriconazole, fluconazole, and posaconazole in 28 patients. Furthermore, a questionnaire was administered to evaluate the patients' opinions of the sampling method. The DBS analytical method showed linearity over the concentration range measured for all triazoles. Results for accuracy and precision were within accepted ranges; samples were stable at room temperature for at least 12 days; and different hematocrit values and blood spot volumes had no significant influence. The ratio of the drug concentration in DBS samples to that in plasma was 1.0 for voriconazole and fluconazole and 0.9 for posaconazole. Sixty percent of the patients preferred DBS analysis as a sampling method; 15% preferred venous blood sampling; and 25% had no preferred method. There was significantly less perception of pain with the DBS sampling method (P= 0.021). In conclusion, DBS analysis is a reliable alternative to venous blood sampling and can be used for therapeutic drug monitoring of voriconazole, fluconazole, and posaconazole. Patients were satisfied with DBS sampling and had less pain than with venous sampling. Most patients preferred DBS sampling to venous blood sampling.

Levetiracetam for Mood Stabilization and Maintenance of Seizure Control Following Multiple Treatment Failures

2005 ◽  
Vol 39 (11) ◽  
pp. 1928-1931 ◽  
Author(s):  
Steven C Stoner ◽  
Jessica W Lea ◽  
Angel L Wolf ◽  
Arnaldo A Berges
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Adverse Events ◽  
Drug Monitoring ◽  
Adverse Reactions ◽  
Seizure Control ◽  
Therapeutic Drug ◽  
Multiple Treatment ◽  
Case Summary ◽  
Mood Stabilization ◽  
Antiepileptic Medications

OBJECTIVE To report the case of a patient who experienced adverse events in succession to antiepileptic medications being used for both antiepileptic and mood-stabilization benefit. CASE SUMMARY A 46-year-old white woman developed hyponatremia with carbamazepine, hyperammonemia with divalproex, cognitive impairment with topiramate, and hyponatremia with oxcarbazepine. The patient was stabilized physically and psychiatrically on levetiracetam without any noted adverse events. DISCUSSION The adverse events in this report have been associated with the medications in question. The patient's presentation is unique, as she developed adverse events in succession to antiepileptic drugs being used to treat both a seizure disorder and symptoms of mood instability. The Naranjo rankings for the reported adverse events indicated the associations were probable (carbamazepine, divalproex, oxcarbazepine) and possible (topiramate). After repeated incidences of intolerability to these drugs, levetiracetam was initiated and provided both seizure control and mood-stabilizing benefits, which eventually led to hospital discharge. CONCLUSIONS Levetiracetam may provide mood-stabilizing qualities through a mechanism that is unique from that of other antiepileptic agents used for their mood-stabilizing properties. There are potential advantages with levetiracetam, as no specific therapeutic drug monitoring parameters need to be followed after its introduction. Additionally, this case emphasizes the importance of therapeutic drug monitoring and frequent assessments to prevent physical and psychiatric adverse reactions.

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