scholarly journals Drug choice and therapeutic drug monitoring in the management of canine primary epilepsy : continuing education

1999 ◽  
Vol 70 (4) ◽  
Author(s):  
T. Vaughan ◽  
J.H. Taylor
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Drug Dosage ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Blood Concentrations ◽  
Paired Samples ◽  
Drug Choice ◽  
Optimal Drug ◽  
Pet Owner

Therapeutic drug monitoring is an underutilised resource in the management of canine primary epilepsy. Many of the anti-epileptic drugs, including phenobarbitone, have variable pharmacokinetic profiles in different dogs, with each individual animal showing variable rates of absorption, distribution, metabolism and excretion. This results in variable serumdrug concentrations with the same oral dose. Many clinicians interpret this situation as therapeutic failure and classify these patients as refractory to treatment. By measuring blood concentrations of drugs at appropriate times, it is possible to explain the efficacy or failure of treatment, and also to prevent serum concentrations from reaching toxic levels. By analysing paired samples, key pharmacokinetic parameters may be calculated for each patient and a profile for the disposition of the drug obtained. Individual optimal drug dosage can be calculated for each patient at little cost to the pet owner.

Immunosuppressant quantification in intravenous microdialysate – towards novel quasi-continuous therapeutic drug monitoring in transplanted patients

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Susanne Weber ◽  
Sara Tombelli ◽  
Ambra Giannetti ◽  
Cosimo Trono ◽  
Mark O’Connell ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Real Time ◽  
Drug Monitoring ◽  
Time Course ◽  
Drug Dosage ◽  
Immunosuppressive Drug ◽  
Therapeutic Drug ◽  
Continuous Sampling ◽  
Real Time Analysis ◽  
Drug Concentrations

AbstractObjectivesTherapeutic drug monitoring (TDM) plays a crucial role in personalized medicine. It helps clinicians to tailor drug dosage for optimized therapy through understanding the underlying complex pharmacokinetics and pharmacodynamics. Conventional, non-continuous TDM fails to provide real-time information, which is particularly important for the initial phase of immunosuppressant therapy, e.g., with cyclosporine (CsA) and mycophenolic acid (MPA).MethodsWe analyzed the time course over 8 h of total and free of immunosuppressive drug (CsA and MPA) concentrations measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in 16 kidney transplant patients. Besides repeated blood sampling, intravenous microdialysis was used for continuous sampling. Free drug concentrations were determined from ultracentrifuged EDTA-plasma (UC) and compared with the drug concentrations in the respective microdialysate (µD). µDs were additionally analyzed for free CsA using a novel immunosensor chip integrated into a fluorescence detection platform. The potential of microdialysis coupled with an optical immunosensor for the TDM of immunosuppressants was assessed.ResultsUsing LC-MS/MS, the free concentrations of CsA (fCsA) and MPA (fMPA) were detectable and the time courses of total and free CsA comparable. fCsA and fMPA and area-under-the-curves (AUCs) in µDs correlated well with those determined in UCs (r≥0.79 and r≥0.88, respectively). Moreover, fCsA in µDs measured with the immunosensor correlated clearly with those determined by LC-MS/MS (r=0.82).ConclusionsThe new microdialysis-supported immunosensor allows real-time analysis of immunosuppressants and tailor-made dosing according to the AUC concept. It readily lends itself to future applications as minimally invasive and continuous near-patient TDM.

Population Pharmacokinetics of Meropenem in Preterm Infants

2021 ◽  
Vol 76 (5) ◽  
pp. 497-505
Author(s):  
Irina B. Bondareva ◽  
Sergey K. Zyryanov ◽  
Aleksandra M. Kazanova
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Pharmacokinetic Parameter ◽  
Gestational Age ◽  
Drug Monitoring ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Variability ◽  
Older Children ◽  
Term Neonates

Background. Meropenem, a broad spectrum carbapenem antibiotic, is often used for newborns despite of limited data available on neonatal pharmacokinetics. Due to pharmacokinetic and pharmacodynamic differences as well as to significant changes in the human body related to growth and maturation of organs and systems, direct scaling and dosing extrapolation from adults or older children with adjustment on patients weight can result in increased risk of toxicity or treatment failures. Aims to evaluate the pharmacokinetics of meropenem in premature neonates based on therapeutic drug monitoring data in real clinical settings. Materials. Of 53 pre-term neonates included in the pharmacokinetic/pharmacodynamic analysis, in 39 (73.6%) patients, gestational age ranged from 23 to 30 weeks. Population and individual pharmacokinetic parameter values were estimated by the NPAG program from the Pmetrics package based on peak-trough therapeutic drug monitoring. Samples were assayed by high-performance liquid chromatography. One-compartment pharmacokinetic model with zero-order input and first-order elimination was used to fit concentration data and to predict pharmacokinetic parameter (%T MIC of free drug) for virtual patients with simulated fast, moderate and slow meropenem elimination received different dosage by minimum inhibitory concentration (MIC) level. Univariate and multivariate regression analysis was used to evaluate the influence of patients covariates (gestational age, postnatal age, postconceptual age, body weight, creatinine clearance calculated by Schwartz formula, etc) on estimated meropenem pharmacokinetic parameters. Results. The identified population pharmacokinetic parameters of meropenem in pre-term newborns (elimination half-lives T1/2 = 1.93 0.341 h; clearance CL = 0.26 0.085 L/h/ kg; volume of distribution V = 0.71 0.22 L/h) were in good agreement with those published in the literature for adults, neonates and older children. Pharmacokinetic/pharmacodynamic modeling demonstrated that a meropenem dosage regimen of 90 mg/kg/day administered using prolonged 3-hour infusion every 8 hours should be considered as potentially effective therapy if nosocomial infections with resistant organisms (MIC 8 mg/L) are treated. Conclusions. Neonates and especially pre-term neonates have a great pharmacokinetic variability. Meropenem dosing in premature newborns derived from population pharmacokinetic/pharmacodynamic model can partly overcome the variability, but not all pharmacokinetic variability can be explained by covariates in a model. Further personalizing based on Bayesian forecasting approach and a patients therapeutic drug monitoring data can help to achieve desired pharmacodynamic target.

Neural and Kernal Methods for Therapeutic Drug Monitoring

2011 ◽  
pp. 238-261 ◽  
Author(s):  
G. Camps-Valls ◽  
J. D. Martin-Guerrero
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Substantial Improvement ◽  
Physical Models ◽  
Therapeutic Drug ◽  
Optimal Dosage ◽  
Blood Concentrations ◽  
Clinical Problems

Recently, important advances in dosage formulations, therapeutic drug monitoring (TDM), and the emerging role of combined therapies have resulted in a substantial improvement in patients’ quality of life. Nevertheless, the increasing amounts of collected data and the non-linear nature of the underlying pharmacokinetic processes justify the development of mathematical models capable of predicting concentrations of a given administered drug and then adjusting the optimal dosage. Physical models of drug absorption and distribution and Bayesian forecasting have been used to predict blood concentrations, but their performance is not optimal and has given rise to the appearance of neural and kernel methods that could improve it. In this chapter, we present a complete review of neural and kernel models for TDM. All presented methods are theoretically motivated, and illustrative examples in real clinical problems are included.

scholarly journals Routine clinical monitoring of sirolimus (rapamycin) whole-blood concentrations by HPLC with ultraviolet detection

1996 ◽  
Vol 42 (12) ◽  
pp. 1943-1948 ◽  
Author(s):  
K L Napoli ◽  
B D Kahan
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Whole Blood ◽  
Clinical Status ◽  
Reversed Phase ◽  
Therapeutic Drug ◽  
Full Time ◽  
Limit Of Quantification ◽  
Blood Concentrations ◽  
Ultraviolet Detection

Abstract During phase I/II clinical trials of sirolimus (rapamycin; SRL), therapeutic drug monitoring was performed with a multistep liquid-liquid extraction of 1-mL aliquots of whole blood followed by reversed-phase HPLC with ultraviolet detection. Blood was sampled according to a standardized protocol and clinical status. SRL concentrations were interpolated from calibration curves with a linear range of 0-50 micrograms/L and 1 microgram/L lower limit of quantification. Quality control was monitored over 68 consecutive analytical runs by using frozen aliquots of SRL-supplemented pooled whole blood at 4, 12, and 32 micrograms/L. These samples showed mean concentrations of 3.7 +/- 0.6, 10.9 +/- 1.1, and 29.6 +/- 2.6 micrograms/L, respectively. This method for therapeutic drug monitoring of SRL permits one full-time technician to analyze 100 clinical specimens per week with a 24-h turnaround time. With this method, a strong linear relation (r2 = 0.946, Sy/x = 0.41, n = 115) between the average SRL concentration over a 24-h period and the SRL concentration at the 24th h was revealed.

Therapeutic Drug Monitoring in Neonates: Problems and Issues

1988 ◽  
Vol 22 (4) ◽  
pp. 317-323 ◽  
Author(s):  
Peter Gal
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Concentration ◽  
Drug Monitoring ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Plasma Drug ◽  
Potential Applications ◽  
Intensive Care Nursery ◽  
Effective Use ◽  
Selection Of

Therapeutic drug monitoring has been applied in several patient populations to promote safer, more effective use of drugs. The development of therapeutic ranges allows clinicians to aim for a plasma drug concentration that is usually safe and effective, and calculation of specific pharmacokinetic parameters allows selection of doses that will achieve the desired plasma concentration. This concept certainly holds true in the intensive care nursery; however, the intensity of monitoring in this setting provides opportunities for far broader application of the information obtained from drug concentration monitoring. This review provides an overview of the complexity of and potential applications for therapeutic drug monitoring in neonates based on literature and clinical experience.

scholarly journals The significance of a new parameter – plasma protein binding – in therapeutic drug monitoring and its application to carbamazepine in epileptic patients

RSC Advances ◽  
2017 ◽  
Vol 7 (45) ◽  
pp. 28048-28055 ◽  
Author(s):  
Jing-lin Gao ◽  
Xin-yu Wang ◽  
Jing An ◽  
Chao-hui Du ◽  
Meng-jiao Li ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Drug Monitoring ◽  
Drug Dosage ◽  
Therapeutic Drug ◽  
Dosage Regimens ◽  
Epileptic Patients

The primary cause of the variability of Cf in pharmacology is the change in plasma protein binding (PPB), thus PPB monitoring should be applied to a better individualization of drug dosage regimens in clinical patients.

scholarly journals Optimum Use of Therapeutic Drug Monitoring and Pharmacokinetics-Pharmacodynamics in the NICU

2009 ◽  
Vol 14 (2) ◽  
pp. 66-74
Author(s):  
Peter Gal
Keyword(s):  
Drug Therapy ◽  
Therapeutic Drug Monitoring ◽  
Antiepileptic Drugs ◽  
Therapeutic Range ◽  
Drug Monitoring ◽  
Population Based ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Patient Response ◽  
Drug Concentrations

Therapeutic drug monitoring is increasingly giving way to dosing drugs based on population-based pharmacokinetic parameters, even when pharmacokinetic values vary quite a bit in individual patients. Further, drug concentrations are often considered appropriate if they are within a defined therapeutic range, even if the patient response is suboptimal. This lecture discusses the limitations of therapeutic ranges in neonates, and proposes greater emphasis on pharmacodynamic curves to individualize drug therapy. Examples are provided using methylxanthines, indomethacin, antiepileptic drugs and aminoglycosides. The potential to use pharmacokinetic findings to describe physiologic changes and occasionally assist with diagnosis is also discussed.

scholarly journals Effect of sample heating on results of therapeutic drug monitoring

2021 ◽  
Vol 45 (3) ◽  
pp. 183-187
Author(s):  
Dao-Hai Cheng ◽  
Zhen-Guang Huang ◽  
Jing-Bing Zhu
Keyword(s):  
Heat Treatment ◽  
Valproic Acid ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Whole Blood ◽  
Plasma Heating ◽  
Therapeutic Drug ◽  
Blood Concentrations ◽  
Therapeutic Drugs ◽  
Drug Concentrations

Abstract Objectives Heat treatment is a convenient measure for pathogens inactivation. The authors investigated the effects of this method on blood concentrations of six commonly therapeutic drugs. Methods Plasma and whole blood were pretreated with or without heating at 56 °C for 30 min, and drug concentrations of vancomycin, methotrexate, valproic acid, digoxin, carbamazepine, and cyclosporine were examined. Results Increased valproic acid levels after plasma heating (63.2 ± 30.2 vs. 62.1 ± 29.8 mg/L, mean recovery 102.0%) and whole blood heating (64.5 ± 30.5 vs. 62.1 ± 29.8 mg/L, mean recovery 104.6%) were observed (both p<0.05), but these differences were not considered clinically important. Recoveries of vancomycin in heat treatments varied widely, with an average and significant decrease of 15.8% in value after whole blood heating (11.7 ± 8.1 vs. 13.7 ± 8.6 mg/L, p<0.05). Conclusions Plasma or whole blood heating at 56 °C for 30 min are feasible in pathogens inactivation during monitoring methotrexate, valproic acid, digoxin, carbamazepine, and cyclosporine. However, such pretreatment seems inappropriate in monitoring vancomycin concentrations. Those results highlight the need for caution when applying heat treatment for pathogens inactivation in therapeutic drug monitoring.

scholarly journals An Aptamer-Based Biosensor for the Azole Class of Antifungal Drugs

mSphere ◽  
2017 ◽  
Vol 2 (4) ◽  
Author(s):  
Gregory R. Wiedman ◽  
Yanan Zhao ◽  
Arkady Mustaev ◽  
Jinglei Ping ◽  
Ramya Vishnubhotla ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Field Effect ◽  
Field Effect Transistor ◽  
Drug Dosage ◽  
Antifungal Drugs ◽  
Therapeutic Drug ◽  
Drug Concentrations ◽  
Graphene Field Effect Transistor ◽  
Effect Transistor

ABSTRACT We have developed the first aptamer directed toward the azole class of antifungal drugs and a functional biosensor for these drugs. This aptamer has a unique secondary structure that allows it to bind to highly hydrophobic drugs. The aptamer works as a capture component of a graphene field effect transistor device. These devices can provide a quick and easy assay for determining drug concentrations. These will be useful for therapeutic drug monitoring of azole antifungal drugs, which is necessary to deal with the complex drug dosage profiles. This technical report describes the development of an aptamer for sensing azole antifungal drugs during therapeutic drug monitoring. Modified synthetic evolution of ligands through exponential enrichment (SELEX) was used to discover a DNA aptamer recognizing azole class antifungal drugs. This aptamer undergoes a secondary structural change upon binding to its target molecule, as shown through fluorescence anisotropy-based binding measurements. Experiments using circular dichroism spectroscopy revealed a unique G-quadruplex structure that was essential and specific for binding to the azole antifungal target. Aptamer-functionalized graphene field effect transistor (GFET) devices were created and used to measure the strength of binding of azole antifungals to this surface. In total, this aptamer and the supporting sensing platform provide a valuable tool for therapeutic drug monitoring of patients with invasive fungal infections. IMPORTANCE We have developed the first aptamer directed toward the azole class of antifungal drugs and a functional biosensor for these drugs. This aptamer has a unique secondary structure that allows it to bind to highly hydrophobic drugs. The aptamer works as a capture component of a graphene field effect transistor device. These devices can provide a quick and easy assay for determining drug concentrations. These will be useful for therapeutic drug monitoring of azole antifungal drugs, which is necessary to deal with the complex drug dosage profiles.

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