scholarly journals Therapeutic Drug Monitoring and Individualized Medicine of Dasatinib: Focus on Clinical Pharmacokinetics and Pharmacodynamics

2021 ◽  
Vol 12 ◽  
Author(s):  
Shiyu He ◽  
Jialu Bian ◽  
Qianhang Shao ◽  
Ying Zhang ◽  
Xu Hao ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Clinical Decision Making ◽  
Lymphoblastic Leukemia ◽  
Individualized Medicine ◽  
Philadelphia Chromosome ◽  
Therapeutic Drug ◽  
Term Survival ◽  
Clinical Pharmacokinetics ◽  
Increased Risk

Dasatinib is an oral second-generation tyrosine kinase inhibitor known to be used widely in Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) and Ph+ acute lymphoblastic leukemia (ALL). Notably, although a high pharmacokinetic variability in patients and an increased risk of pleural effusion are attendant, fixed dosing remains standard practice. Retrospective studies have suggested that dasatinib exposure may be associated with treatment response (efficacy/safety). Therapeutic drug monitoring (TDM) is gradually becoming a practical tool to achieve the goal of individualized medicine for patients receiving targeted drugs. With the help of TDM, these patients who maintain response while have minimum adverse events may achieve long-term survival. This review summaries current knowledge of the clinical pharmacokinetics variation, exposure-response relationships and analytical method for individualized dosing of dasatinib, in particular with respect to therapeutic drug monitoring. In addition, it highlights the emerging insights into several controversial issues in TDM of dasatinib, with the aim of presenting up-to-date evidence for clinical decision-making and insights for future studies.

Clinical pharmacokinetics and therapeutic drug monitoring of sirolimus

2000 ◽  
Vol 22 ◽  
pp. B101-B121 ◽  
Author(s):  
Allan MacDonald ◽  
Joseph Scarola ◽  
James T. Burke ◽  
James J. Zimmerman
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Clinical Pharmacokinetics

Therapeutic drug monitoring in neonates

2016 ◽  
Vol 101 (4) ◽  
pp. 377-381 ◽  
Author(s):  
Steven Pauwels ◽  
Karel Allegaert
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Whole Body ◽  
Matrix Composition ◽  
Therapeutic Drug ◽  
Dosing Regimens ◽  
Body Cooling ◽  
Whole Body Cooling

Therapeutic drug monitoring (TDM) aims to integrate drug measurement results into clinical decision making. The basic rules apply when using TDM in neonates (aminoglycosides, vancomycin, phenobarbital, digoxin), but additional factors should also be taken into account. First, due to both pharmacokinetic variability and non-pharmacokinetic factors, the correlation between dosage and concentration is poor in neonates, but can be overcome with the use of more complex, validated dosing regimens. Second, the time to reach steady state is prolonged, especially when no loading dose is used. Consequently, the timing of TDM sampling is important in this population. Third, the target concentration may be uncertain (vancomycin) or depend on specific factors (phenobarbital during whole body cooling). Finally, because of differences in matrix composition (eg, protein, bilirubin), assay-related inaccuracies may be different in neonates. We anticipate that complex validated dosing regimens, with subsequent TDM sampling and Bayesian forecasting, are the next step in tailoring pharmacotherapy to individual neonates.

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 Chronopharmacology in Therapeutic Drug Monitoring—Dependencies between the Rhythmics of Pharmacokinetic Processes and Drug Concentration in Blood

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1915
Author(s):  
Lukasz Dobrek
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Age Groups ◽  
Therapeutic Drug ◽  
Physiological Conditions ◽  
Drug Concentrations ◽  
Increased Risk ◽  
Drugs In Blood ◽  
Treatment Individualization ◽  
The Given

The objective of the optimization of pharmacotherapy compliant with the basic rules of clinical pharmacology is its maximum individualization, ensuring paramount effectiveness and security of the patient’s therapy. Thus, multiple factors that are decisive in terms of uniqueness of treatment of the given patient must be taken into consideration, including, but not limited to, the patient’s age, sex, concomitant diseases, special physiological conditions (e.g., pregnancy, lactation, extreme age groups), polypharmacotherapy and polypragmasia (particularly related to increased risk of drug interactions), and patient’s phenotypic response to the administered drug with possible genotyping. Conducting therapy while monitoring the concentration of certain drugs in blood (Therapeutic Drug Monitoring; TDM procedure) is also one of the factors enabling treatment individualization. Furthermore, another material, and yet still a marginalized pharmacotherapeutic factor, is chronopharmacology, which indirectly determines the values of drug concentrations evaluated in the TDM procedure. This paper is a brief overview of chronopharmacology, especially chronopharmacokinetics, and its connection with the clinical interpretation of the meaning of the drug concentrations determined in the TDM procedure.

Clinical Pharmacokinetics versus Therapeutic Drug Monitoring — A Perspective for Pharmacists

1981 ◽  
Vol 15 (6) ◽  
pp. 474-475
Author(s):  
Paul A. Kramer
Keyword(s):  
Drug Therapy ◽  
Therapeutic Drug Monitoring ◽  
Clinical Pharmacokinetic ◽  
Drug Monitoring ◽  
Patient Management ◽  
Drug Level ◽  
Therapeutic Drug ◽  
Clinical Pharmacokinetics

The classical role of the pharmacist in providing clinical pharmacokinetic services is reviewed and contrasted with the role in drug level interpretation now being assumed by many laboratory analysts. Arguments are presented for better articulation of the pharmacist's role and improved utilization of his unique knowledge of drug therapy in the application of drug level determinations to patient management. Without an increased presence in clinical pharmacokinetics, other professionals, less appropriately trained, may fill a substantial void which has recently developed in this important area of drug therapy.

scholarly journals Therapeutic Drug Monitoring of Biologics in IBD: Essentials for the Surgical Patient

2021 ◽  
Vol 10 (23) ◽  
pp. 5642
Author(s):  
Rodrigo Bremer Nones ◽  
Phillip R. Fleshner ◽  
Natalia Sousa Freitas Queiroz ◽  
Adam S. Cheifetz ◽  
Antonino Spinelli ◽  
...  
Keyword(s):  
Postoperative Complications ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Quality Data ◽  
Therapeutic Drug ◽  
Surgical Patient ◽  
Serum Concentrations ◽  
Drug Concentrations ◽  
Clinical Scenarios ◽  
Increased Risk

Despite significant development in the pharmacological treatment of inflammatory bowel diseases (IBD) along with the evolution of therapeutic targets and treatment strategies, a significant subset of patients still requires surgery during the course of the disease. As IBD patients are frequently exposed to biologics at the time of abdominal and perianal surgery, it is crucial to identify any potential impact of biological agents in the perioperative period. Even though detectable serum concentrations of biologics do not seem to increase postoperative complications after abdominal procedures in IBD, there is increasing evidence on the role of therapeutic drug monitoring (TDM) in the perioperative setting. This review aims to provide a comprehensive summary of published studies reporting the association of drug concentrations and postoperative outcomes, postoperative recurrence (POR) after an ileocolonic resection for Crohn’s disease (CD), colectomy rates in ulcerative colitis (UC), and perianal fistulizing CD outcomes in patients treated with biologics. Current data suggest that serum concentrations of biologics are not associated with an increased risk in postoperative complications following abdominal procedures in IBD. Moreover, higher concentrations of anti-TNF agents are associated with a reduction in colectomy rates in UC. Finally, higher serum drug concentrations are associated with reduced rates of POR after ileocolonic resections and increased rates of perianal fistula healing in CD. TDM is being increasingly used to guide clinical decision making with favorable outcomes in many clinical scenarios. However, given the lack of high quality data deriving mostly from retrospective studies, the evidence supporting the systematic application of TDM in the perioperative setting is still inconclusive.

The impact of ethnic miscegenation on tacrolimus clinical pharmacokinetics and therapeutic drug monitoring

2002 ◽  
Vol 16 (4) ◽  
pp. 262-272 ◽  
Author(s):  
Claudia R Felipe ◽  
Helio T Silva ◽  
Paula GP Machado ◽  
Riberto Garcia ◽  
Silvia R Da Silva Moreira ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Clinical Pharmacokinetics ◽  
The Impact
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