Saliva versus Plasma Therapeutic Drug Monitoring of Gentamicin in Jordanian Preterm Infants. Development of a Physiologically-Based Pharmacokinetic (PBPK) Model and Validation of Class II Drugs of Salivary Excretion Classification System

Drug Research ◽  
2020 ◽  
Vol 70 (10) ◽  
pp. 455-462
Author(s):  
Nasir Idkaidek ◽  
Salim Hamadi ◽  
Rabab Bani-Domi ◽  
Ibrahim Al-Adham ◽  
Motasem Alsmadi ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Adverse Effects ◽  
Preterm Infant ◽  
Preterm Infants ◽  
Drug Monitoring ◽  
Pbpk Model ◽  
Therapeutic Drug ◽  
Non Invasive ◽  
Physiologically Based Pharmacokinetic ◽  
Physiologically Based

AbstractGentamicin has proven to be a very successful treatment for bacterial infection, but it also can cause adverse effects, especially ototoxicity, which is irreversible. Therapeutic drug monitoring (TDM) in saliva is a more convenient non-invasive alternative compared to plasma. A physiologically-based pharmacokinetic (PBPK) model of gentamicin was built and validated using previously-published plasma and saliva data. The validated model was then used to predict experimentally-observed plasma and saliva gentamicin TDM data in Jordanian pediatric preterm infant patients measured using sensitive LCMS/MS method. A correlation was established between plasma and saliva exposures. The developed PBPK model predicted previously reported gentamicin levels in plasma, saliva and those observed in the current study. A good correlation was found between plasma and saliva exposures. The PBPK model predicted that gentamicin in saliva is 5–7 times that in plasma, which is in agreement with observed results. Saliva can be used as an alternative for TDM of gentamicin in preterm infant patients. Exposure to gentamicin in plasma and saliva can reliably be predicted using the developed PBPK model in patients.

Use of Saliva in Therapeutic Drug Monitoring of Caffeine in Preterm Infants

2001 ◽  
Vol 23 (3) ◽  
pp. 250-254 ◽  
Author(s):  
Saskia N. de Wildt ◽  
Katja T. M. Kerkvliet ◽  
Muriël G. A. Wezenberg ◽  
Sabine Ottink ◽  
Wim C. J. Hop ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Preterm Infants ◽  
Drug Monitoring ◽  
Therapeutic Drug

scholarly journals Caffeine for the Pharmacological Treatment of Apnea of Prematurity in the NICU: Dose Selection Conundrum, Therapeutic Drug Monitoring and Genetic Factors

2021 ◽  
Vol 12 ◽  
Author(s):  
Jia-Yi Long ◽  
Hong-Li Guo ◽  
Xin He ◽  
Ya-Hui Hu ◽  
Ying Xia ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Clinical Response ◽  
Preterm Infants ◽  
Drug Monitoring ◽  
Pharmacological Treatment ◽  
Interindividual Variability ◽  
Standard Dose ◽  
Therapeutic Drug ◽  
Safety And Efficacy ◽  
Apnea Of Prematurity

Caffeine citrate is the drug of choice for the pharmacological treatment of apnea of prematurity. Factors such as maturity and genetic variation contribute to the interindividual variability in the clinical response to caffeine therapy in preterm infants, making the optimal dose administered controversial. Moreover, the necessity for therapeutic drug monitoring (TDM) of caffeine is still worth discussing due to the need to achieve the desired target concentrations as well as concerns about the safety of higher doses. Therefore, we reviewed the pharmacokinetic profile of caffeine in preterm infants, evidence of the safety and efficacy of different doses of caffeine, therapeutic concentration ranges of caffeine and impact of genetic variability on caffeine therapy. Whereas the safety and efficacy of standard-dose caffeine have been demonstrated, evidence for the safety of higher administered doses is insufficient. Thus, preterm infants who lack clinical response to standard-dose caffeine therapy are of interest for TDM when dose optimization is performed. Polymorphisms in pharmacodynamics-related genes, but not in pharmacokinetics-related genes, have a significant impact on the interindividual variability in clinical response to caffeine therapy. For preterm infants lacking clinical response, how to develop individualized medication regimens for caffeine remains to be explored.

scholarly journals Clinical utility of therapeutic drug monitoring of antiepileptic drugs

2019 ◽  
Vol 10 (4) ◽  
pp. 344-355 ◽  
Author(s):  
Zanab Al-Roubaie ◽  
Elena Guadagno ◽  
Agnihotram V. Ramanakumar ◽  
Afsheen Q. Khan ◽  
Kenneth A. Myers
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Adverse Effects ◽  
Antiepileptic Drugs ◽  
Drug Monitoring ◽  
Seizure Control ◽  
Therapeutic Drug ◽  
Seizure Outcome ◽  
Randomized Controlled ◽  
Patient Reported ◽  
Positive Effect

ObjectiveTo systematically review and evaluate the available evidence supporting or refuting clinical use of therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) in patients with epilepsy.MethodsWe searched MEDLINE, Embase, BIOSIS, Cochrane, PubMed, Africa-Wide Information, Web of Science, and grey literature. Randomized controlled studies and observational studies that compared the clinical outcomes of TDM vs non-TDM were included. Two reviewers independently extracted the data. The primary outcome was seizure control; adverse effects were considered as secondary outcomes. The PROSPERO ID of this systematic review's protocol is CRD42018089925.ResultsSixteen studies were identified meeting eligibility requirements. Four randomized controlled trials (RCTs), 1 meta-analysis, and 11 quasiexperimental (QE) studies were included in the systematic review. Results from the analysis of RCTs showed no significant positive effect of TDM on seizure outcome (only 25% positive effect of phenytoin). However, some of the QE studies found that TDM was associated with better seizure control or lower rates of adverse effects. The existing evidence from various designs has shown various methodological implications, which warrants inconclusive results and highlights the requirement of more number of studies in this line.ConclusionsIf optimally implemented, TDM may enhance clinical care, particularly for phenytoin and other AEDs with complex pharmacokinetics. However, the ideal method for implementation is unclear, and serum drug levels should be considered in context with patient-reported clinical data regarding seizure control and adverse events.

scholarly journals Comparing Predictions of a PBPK Model for Cyclosporine With Drug Levels From Therapeutic Drug Monitoring

2021 ◽  
Vol 12 ◽  
Author(s):  
Sonja E. Zapke ◽  
Stefan Willmann ◽  
Scott-Oliver Grebe ◽  
Kristin Menke ◽  
Petra A. Thürmann ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Pbpk Model ◽  
Clinical Population ◽  
Pbpk Modeling ◽  
Additional Patient ◽  
Therapeutic Drug ◽  
Model Parameters ◽  
Drug Levels ◽  
Trough Levels

This study compared simulations of a physiologically based pharmacokinetic (PBPK) model implemented for cyclosporine with drug levels from therapeutic drug monitoring to evaluate the predictive performance of a PBPK model in a clinical population. Based on a literature search model parameters were determined. After calibrating the model using the pharmacokinetic profiles of healthy volunteers, 356 cyclosporine trough levels of 32 renal transplant outpatients were predicted based on their biometric parameters. Model performance was assessed by calculating absolute and relative deviations of predicted and observed trough levels. The median absolute deviation was 6 ng/ml (interquartile range: 30 to 31 ng/ml, minimum = −379 ng/ml, maximum = 139 ng/ml). 86% of predicted cyclosporine trough levels deviated less than twofold from observed values. The high intra-individual variability of observed cyclosporine levels was not fully covered by the PBPK model. Perspectively, consideration of clinical and additional patient-related factors may improve the model’s performance. In summary, the current study has shown that PBPK modeling may offer valuable contributions for pharmacokinetic research in clinical drug therapy.

Design and development of a suitable adsorbent to capture theophylline for non-invasive therapeutic drug monitoring with exhaled breath

2015 ◽  
Vol 7 (2) ◽  
pp. 423-427
Author(s):  
A. Yamamoto ◽  
S. Hioki ◽  
C. Tanada ◽  
T. Miwa ◽  
Y. Inoue ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Blood Plasma ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Exhaled Breath ◽  
Design And Development ◽  
Non Invasive

The possibility of using exhaled breath as a substitute for blood/plasma in areas of therapeutic drug monitoring was investigated.

scholarly journals A Non-Invasive Method for Detection of Antihypertensive Drugs in Biological Fluids: The Salivary Therapeutic Drug Monitoring

2022 ◽  
Vol 12 ◽  
Author(s):  
Valeria Avataneo ◽  
Elvira Fanelli ◽  
Amedeo De Nicolò ◽  
Franco Rabbia ◽  
Alice Palermiti ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Antihypertensive Drugs ◽  
Biological Fluids ◽  
Real Life ◽  
European Medicines Agency ◽  
Therapeutic Drug ◽  
Hypertensive Patients ◽  
Non Invasive ◽  
Target Values

Objectives: Arterial hypertension is still the most frequent cause of cardiovascular and cerebrovascular morbidity and mortality. Antihypertensive treatment has proved effective in reduction of cardiovascular risk. Nevertheless, lifestyle interventions and pharmacological therapy in some cases are ineffective in reaching blood pressure target values, despite full dose and poly-pharmacological treatment. Poor adherence to medications is an important cause of treatment failure. Different methods to assess therapeutic adherence are currently available: Therapeutic drug monitoring in biological fluids has previously demonstrated its efficacy and reliability. Plasma and urine have been already used for this purpose, but they may be affected by some practical limitations. Saliva may represent a feasible alternative.Methods: Fourteen antihypertensive drugs and two metabolites were simultaneously tested in plasma, urine, and saliva. Tested molecules included: atenolol, nebivolol, clonidine, ramipril, olmesartan, telmisartan, valsartan, amlodipine, nifedipine, doxazosin, chlorthalidone, hydrochlorothiazide, indapamide, sacubitril, ramiprilat, and sacubitrilat. Therapeutic drug monitoring was performed using ultra-high performance liquid chromatography, coupled to tandem mass spectrometry (UHPLC-MS/MS). The method has been preliminarily evaluated in a cohort of hypertensive patients.Results: The method has been validated according to US Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines. The application on a cohort of 32 hypertensive patients has demonstrated sensibility and specificity of 98% and 98.1%, respectively, with a good feasibility in real-life clinical practice.Conclusion: Saliva may represent a feasible biological sample for therapeutic drug monitoring by non-invasive collection, prompt availability, and potential accessibility also in out-of-clinic settings.

Therapeutic drug monitoring of caffeine in preterm infants: Could saliva be an alternative to serum?

Therapies ◽  
2017 ◽  
Vol 72 (6) ◽  
pp. 685-689 ◽  
Author(s):  
Amel Chaabane ◽  
Fatma Z. Chioukh ◽  
Zohra Chadli ◽  
Nadia Ben Fredj ◽  
Karim Ben Ameur ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Preterm Infants ◽  
Drug Monitoring ◽  
Therapeutic Drug
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