scholarly journals Vincristine dosing, drug exposure and therapeutic drug monitoring in neonate and infant cancer patients

2021 ◽  
Author(s):  
Shelby Barnett ◽  
Farina Hellmann ◽  
Elizabeth Parke ◽  
Guy Makin ◽  
Deborah A. Tweddle ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Cancer Patients ◽  
Drug Monitoring ◽  
Drug Exposure ◽  
Therapeutic Drug

scholarly journals P346 Single-centre experience of ustekinumab: Therapeutic drug monitoring in Crohn’s disease patients

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S331-S333
Author(s):  
C Liefferinckx ◽  
M Fassin ◽  
D Thomas ◽  
C Minsart ◽  
A Cremer ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Therapeutic Drug Monitoring ◽  
Crohn's Disease ◽  
Median Time ◽  
Real World ◽  
Drug Monitoring ◽  
Drug Exposure ◽  
Therapeutic Drug ◽  
Loss Of Response

Abstract Background Therapeutic drug monitoring (TDM) is a diagnostic tool in the monitoring of anti-TNF therapies. Yet, the benefit for TDM of new biologics such as ustekinumab (USK) is still controversial in real-world experiences. Methods This monocentric retrospective study aims to correlate USK trough levels (TLs) with clinical and endoscopic data. All patients have given written consent to the Biobank (B2011/005). Endoscopic disease was defined as quiescent in absence of endoscopic lesions, mild disease in presence of few superficial ulcerations, moderate in presence of several ulcers and severe in presence of numerous deep ulcers and/or inflammatory stenosis. 313 serum USK samples from 67 Crohn’s disease patients were used to measure USK TL (USK ELISA, apDia) while 88 samples (at week 16, and before and after optimisation) were used to measure anti-drug antibody (ADA), using a drug-tolerant affinity capture elution anti-ustekinumab assay Results Demographic and baseline data of our population are presented in Table 1. The median follow-up was 73 weeks (IQR 39–92). An optimisation due to loss of response was required in 44.8% of patients (n = 30) after a median time of 38 weeks (IQR 24–55). To evaluate the drug efficacy, an endoscopy was performed in 61% of cases at a median time of 35 weeks (IQR 27–47). TLs were 5.2 µg/ml (IQR 2.1–8.8), 1.7 µg/ml (IQR 0.3–4.3) and 2.6 µg/ml (IQR 0.6–4.1) at week 8, 16 and 24, respectively. TLs at week 8 were correlated to the induction IV dose administrated (r = 0.3, p = 0.03). At week 16, low TLs were associated with higher endoscopic activity in the follow-up (p = 0.02), although this was not the case at week 8 (p = 0.5) (Figure 1). Patients not requiring an optimisation had higher TLs in maintenance than patients requiring optimisation (2.45 µg/ml (IQR 1.3–4.4) vs. 1.15 µg/ml (IQR 0.1–2.24), p = 0.008). Obviously, optimisation significantly increased TLs (1.15 µg/ml (IQR 0.1–2.24) vs. 6.6 µg/ml (IQR 2.3–11.3), p < 0.001). ADA were undetectable in all the measured samples in maintenance. Conclusion This real-world experience confirms a drug exposure-endoscopic response relationship. Week 16 seems to be an appropriate time point to monitor drug exposure. Earlier USK TLs, at week 8, appear less valuable to be monitored due to the influence of initial IV dose. The absence of immunogenicity suggests that it is not a key driver in the loss of response.

Importance of voriconazole therapeutic drug monitoring in pediatric cancer patients with invasive aspergillosis

2012 ◽  
Vol 60 (1) ◽  
pp. 82-87 ◽  
Author(s):  
Soo-Han Choi ◽  
Soo-Youn Lee ◽  
Ji-Young Hwang ◽  
Soo Hyun Lee ◽  
Keon Hee Yoo ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Invasive Aspergillosis ◽  
Cancer Patients ◽  
Pediatric Cancer ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Pediatric Cancer Patients

scholarly journals Model-Optimized Fluconazole Dose Selection for Critically Ill Patients Improves Early Pharmacodynamic Target Attainment without the Need for Therapeutic Drug Monitoring

2020 ◽  
Vol 65 (3) ◽  
Author(s):  
Indy Sandaradura ◽  
Jessica Wojciechowski ◽  
Deborah J. E. Marriott ◽  
Richard O. Day ◽  
Sophie Stocker ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Critically Ill ◽  
Drug Monitoring ◽  
Critically Ill Patients ◽  
Drug Exposure ◽  
Fungal Infections ◽  
Therapeutic Drug ◽  
Target Attainment ◽  
Dose Selection ◽  
Dose Individualization

ABSTRACT Fluconazole has been associated with higher mortality compared with the echinocandins in patients treated for invasive candida infections. Underexposure from current fluconazole dosing regimens may contribute to these worse outcomes, so alternative dosing strategies require study. The objective of this study was to evaluate fluconazole drug exposure in critically ill patients comparing a novel model-optimized dose selection method with established approaches over a standard 14-day (336-h) treatment course. Target attainment was evaluated in a representative population of 1,000 critically ill adult patients for (i) guideline dosing (800-mg loading and 400-mg maintenance dosing adjusted to renal function), (ii) guideline dosing followed by therapeutic drug monitoring (TDM)-guided dose adjustment, and (iii) model-optimized dose selection based on patient factors (without TDM). Assuming a MIC of 2 mg/liter, free fluconazole 24-h area under the curve (fAUC24) targets of ≥200 mg · h/liter and <800 mg · h/liter were used for assessment of target attainment. Guideline dosing resulted in underexposure in 21% of patients at 48 h and in 23% of patients at 336 h. The TDM-guided strategy did not influence 0- to 48-h target attainment due to inherent procedural delays but resulted in 37% of patients being underexposed at 336 h. Model-optimized dosing resulted in ≥98% of patients meeting efficacy targets throughout the treatment course, while resulting in less overexposure compared with guideline dosing (7% versus 14%) at 336 h. Model-optimized dose selection enables fluconazole dose individualization in critical illness from the outset of therapy and should enable reevaluation of the comparative effectiveness of this drug in patients with severe fungal infections.

scholarly journals Developing a Nationwide Infrastructure for Therapeutic Drug Monitoring of Targeted Oral Anticancer Drugs: The ON-TARGET Study Protocol

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6281
Author(s):  
Anna Mc Laughlin ◽  
Eduard Schmulenson ◽  
Olga Teplytska ◽  
Sebastian Zimmermann ◽  
Patrick Opitz ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Anticancer Drugs ◽  
Drug Monitoring ◽  
Drug Exposure ◽  
Plasma Concentrations ◽  
Blood Sampling ◽  
Therapeutic Drug ◽  
Study Phase ◽  
Blood Samples ◽  
Drug Concentrations

Exposure-efficacy and/or exposure-toxicity relationships have been identified for up to 80% of oral anticancer drugs (OADs). Usually, OADs are administered at fixed doses despite their high interindividual pharmacokinetic variability resulting in large differences in drug exposure. Consequently, a substantial proportion of patients receive a suboptimal dose. Therapeutic Drug Monitoring (TDM), i.e., dosing based on measured drug concentrations, may be used to improve treatment outcomes. The prospective, multicenter, non-interventional ON-TARGET study (DRKS00025325) aims to investigate the potential of routine TDM to reduce adverse drug reactions in renal cell carcinoma patients receiving axitinib or cabozantinib. Furthermore, the feasibility of using volumetric absorptive microsampling (VAMS), a minimally invasive and easy to handle blood sampling technique, for sample collection is examined. During routine visits, blood samples are collected and sent to bioanalytical laboratories. Venous and VAMS blood samples are collected in the first study phase to facilitate home-based capillary blood sampling in the second study phase. Within one week, the drug plasma concentrations are measured, interpreted, and reported back to the physician. Patients report their drug intake and toxicity using PRO-CTCAE-based questionnaires in dedicated diaries. Ultimately, the ON-TARGET study aims to develop a nationwide infrastructure for TDM for oral anticancer drugs.

scholarly journals Advances in Therapeutic Drug Monitoring in Biologic Therapies for Pediatric Inflammatory Bowel Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Akshay Kapoor ◽  
Eileen Crowley
Keyword(s):  
Inflammatory Bowel Disease ◽  
Therapeutic Drug Monitoring ◽  
Bowel Disease ◽  
Drug Monitoring ◽  
Drug Exposure ◽  
Therapeutic Drug ◽  
Dose Individualization ◽  
Loss Of Response ◽  
Fixed Weight ◽  
Inflammatory Bowel

In the current era of treat-to-target strategies, therapeutic drug monitoring (TDM) has emerged as a potential tool in optimizing the efficacy of biologics for children diagnosed with inflammatory bowel disease (IBD). The incorporation of TDM into treatment algorithms, however, has proven to be complex. “Proactive” TDM is emerging as a therapeutic strategy due to a recently published pediatric RCT showing a clear benefit of “proactive” TDM in anti-TNF therapy. However, target therapeutic values for different biologics for different disease states [ulcerative colitis (UC) vs. Crohn's disease (CD)] and different periods of disease activity (induction vs. remission) require further definition. This is especially true in pediatrics where the therapeutic armamentarium is limited, and fixed weight-based dosing may predispose to increased clearance leading to decreased drug exposure and subsequent loss of response (pharmacokinetic and/or immunogenic). Model-based dosing for biologics offers an exciting insight into dose individualization thereby minimizing the chances of losing response. Similarly, point-of-care testing promises real-time assessment of drug levels and individualized decision-making. In the current clinical realm, TDM is being used to prolong drug durability and efficacy and prevent loss of response. Ongoing innovations may transform it into a personalized tool to achieve optimal therapeutic endpoints.

Population Pharmacokinetic (PK) Modeling of Hydroxyurea for Therapeutic Drug Monitoring Applications in Children and Adolescents with Sickle Cell Disease

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2136-2136
Author(s):  
Pawel Wiczling ◽  
Robert I. Liem ◽  
Julie A. Panepinto ◽  
Uttam Garg ◽  
Susan M. Abdel-Rahman ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Sickle Cell ◽  
Drug Monitoring ◽  
Drug Exposure ◽  
Oral Drug ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Average Dose ◽  
Intersubject Variability ◽  
Exposure Response

Abstract Abstract 2136 Introduction: Sickle cell anemia (SCA) is an inherited disorder of abnormal hemoglobin synthesis. Hydroxyurea (HU) is the only disease modifying agent available for use in patients with SCA. Clinically, HU has been shown to decrease pain, number of transfusions, and development of acute chest syndrome as well as improve life expectancy in adults with SCA. Although HU is increasingly utilized to treat children with SCA, drug exposure-response relationships and therapeutic drug monitoring are not well characterized in the pediatric population. The exposure-response relationships of HU are currently being evaluated as is the potential role of therapeutic drug monitoring. Objective: The objective of this study was to develop a population pharmacokinetic (PK) model sufficient to describe HU disposition in serum and urine following oral drug administration in pediatric patients. Such a model is required for exploring concentration-effect relationships in children with SCA taking HU. Methods: PK was determined in 20 subjects (mean age 10.5 yr, range 5–17 yr) with SCA either as a single dose (SD, n=6, average dose 17.4 mg/kg) or at steady state (SS, n=14, average daily dose 25.5 mg/kg). Blood and urine samples for HU assay were taken throughout the 24 hour period post HU administration. HU was quantitated by a validated gas chromatography–mass spectrometry (GC-MS) method. Population nonlinear mixed-effect modeling was done using NONMEM software. Measured HU concentrations at specific sampling time points were compared to model predicted area under the curves (AUCs) to find the most predictive relationship. Results: A one-compartment model with first-order absorption and two elimination pathways (metabolic and renal) was used. The mean absorption rate constant differed for children < 8.5 years of age (19.5 h−1) as compared to those ≥ 8.5 years of age (2.1 h−1) and demonstrated high intersubject variability (76%). The population apparent volume of distribution (V/F) was 21.3 L (for an average weight patient of 30.7 kg) with an intersubject variability of 24.7%. The apparent renal (CLu/F) and metabolic (CLm/F) clearance was 3.47 L/hr and 3.52 L/hr, respectively, with the same between subject variability of 42%. Significant relationships (p<0.005) between both CL/F and V/F and body weight were found with these parameters increasing by 2.96% and 2.49%, respectively, for every kilogram difference from the median weight. Significant linear correlations were apparent between the plasma HU concentration at 0.75, 1, 1.5, 2, 4, and 6 hours post-dose; the most significant (p<0.01, r2 =0.71) occurring at 1.5 hours. Conclusion: In children with SCA, a population PK model parameterized from a classical PK study of HU was successful in describing HU disposition in plasma and urine. Data from the model also demonstrated that HU plasma concentrations at 1.5 or 2 hours after an oral dose of the drug were especially predictive of systemic drug exposure (as reflected by AUC). Data from this study also suggest that there may be age related differences in absorption rates. Further studies are warranted to confirm this finding. Disclosures: Off Label Use: Hydroxyurea is not labeled for use in children.

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