SYMPOSIUM 14: Target Concentrations, Time to Reach Target, Days in Target: Therapeutic Target Parameters
Tracks
Track 2
| Tuesday, September 23, 2025 |
| 3:30 PM - 5:00 PM |
| Grand Copthorne Waterfront Hotel - Waterfront Ballroom I |
Details
Attainment of anti-infective concentrations within therapeutic range is widely accepted as the outcome of Therapeutic Drug Monitoring (TDM). Several randomized control trials considering the achievement of therapeutic range as the outcome of TDM intervention could not demonstrate any advantage or could demonstrate only a marginal advantage of TDM strategies in improving clinical outcomes. Inclusion of time to reach target and days in target as parameters of therapeutic target in addition to attainment of target concentrations may considerably improve patient outcome. This symposium will explore strategies to achieve these three goals of TDM and will suggest how to integrate all these goals as an intervention while performing clinical trials.
Speaker
Dr Lee Lee Low
Infectious Disease Physician / Head of Department
Hospital Sultanah Bahiyah
The Impact of Inter-individual variation of anti-infective drug exposure and delay in achieving the target concentration on clinical outcome
Abstract
The inter-individual variability of anti-infective agents arises from both pharmacokinetics (PK) and pharmacodynamics (PD) of the drugs. Integrating PK and PD is essential to define the dose-exposure-response relationship, which plays a critical role in maximizing efficacy,
preventing toxicity and reducing the risk of drug resistance. Optimizing antibiotic doses in critically ill patients is particularly challenging due to the significant inter-patient variability, even for drugs with linear PK. Critical illness has been linked to reduced anti-infective exposure, and delays in achieving the target drug concentration may lead to inadequate clinical response and the development of drug resistance. This lecture aims to highlight and present clinical evidence supporting dose optimization as a strategy to mitigate interpatient pharmacokinetic variability, and to improve treatment outcome.
preventing toxicity and reducing the risk of drug resistance. Optimizing antibiotic doses in critically ill patients is particularly challenging due to the significant inter-patient variability, even for drugs with linear PK. Critical illness has been linked to reduced anti-infective exposure, and delays in achieving the target drug concentration may lead to inadequate clinical response and the development of drug resistance. This lecture aims to highlight and present clinical evidence supporting dose optimization as a strategy to mitigate interpatient pharmacokinetic variability, and to improve treatment outcome.
Biography
Dr Lee Lee Low is an Infectious Disease Physician and Head of the Department of Medicine at Hospital Sultanah Bahiyah, Alor Setar, Kedah, Malaysia. She is also the Chief Coordinator of Infection Control and Antimicrobial Stewardship (AMS) program for the state of Kedah, Malaysia.
Dr Low currently sits on the committee of the Asia Fungal Working Group, under the International Society for Human and Animal Mycology (ISHAM). She is also involved in various societies in Malaysia, including the Malaysian Society of HIV Medicine, the Malaysian Society of Infectious Disease and Chemotherapy, The Malaysian Society of Infection Control and Infectious Diseases, and IATDMCT.
An avid researcher, Dr Low has served as the co-investigator of several major studies in the field of infectious diseases and has published many peer-reviewed articles on the subject.
Dr Anne-Grete MÃrtson
University of Leiden
Use of dose optimization programs in achieving target anti-infective drug concentrations early and maintaining it for the duration of anti-infective drug treatment
Abstract
Achieving optimal tissue penetration and maintaining therapeutic concentrations of anti-infective agents are critical for successful treatment. Dose optimization integrating pharmacokinetic/pharmacodynamic (PK/PD) principles, patient-specific variables and therapeutic drug monitoring (TDM) are needed to improve drug distribution to infection sites. Utilizing model-informed precision dosing (MIPD) provides a systematic approach to optimizing drug therapy. This method incorporates population PK/PD modeling, while also integrating patient-specific covariates (e.g., age, weight, disease state) to guide treatment optimization. This talk will explore MIPD and other modelling approaches that are used for dose optimisation, with a focus on maintaining effective drug levels in target tissues, ultimately supporting optimized treatment of infectious diseases.
Biography
Anne-Grete Märtson is an assistant professor at the Leiden Academic Centre for Drug Research, Leiden University. She is leading a research group focusing on translational antiviral pharmacology. The group focuses on clinical studies, laboratory experiments such as the hollow fibre infection model and use computational methods to find best treatment regimens and translate results back to the clinical setting. The research topics include optimizing ganciclovir therapy for cytomegalovirus (CMV), therapeutic drug monitoring of antivirals, relating antiviral drug exposure to dose-related toxicity, dosing in extremes of organ function and in special populations, delay in antiviral therapy in SARS-CoV-2.
Prof Birgit Koch
Erasmus MC Rotterdam
Strategies to Improve Therapeutic Target Attainment for Anti-Infectives: Leveraging Advanced Tools and Technologies
Abstract
Achieving optimal therapeutic target attainment in anti-infective therapy is essential for maximizing efficacy, reducing toxicity, and minimizing the development of resistance. This session will explore innovative strategies that aim to improve the precision of anti-infective dosing through the integration of advanced technologies and methodologies.
Goals/Objectives:
1. Understand the Role of Therapeutic Drug Monitoring (TDM) in individualizing dosing and improving patient outcomes by adjusting drug levels for optimal therapeutic response.
2. Explore Model-Informed Precision Dosing (MIPD) as a cutting-edge approach to predict individualized drug doses based on pharmacokinetic (PK) models and patient-specific data, ensuring better efficacy and safety.
3. Examine the Importance of Target Site Concentrations in achieving effective drug exposure at the site of infection, highlighting the need for enhanced PK models that incorporate tissue penetration data.
4. Discuss Alternative Sampling Techniques such as saliva and dried blood spots, offering less invasive and more frequent options for monitoring anti-infective drug concentrations.
5. Delve into the Potential of Improved PK Models and how they can provide more accurate dosing recommendations through population-based approaches and dynamic modeling.
6. Review the Future of Machine Learning and Real-Time Monitoring, which could revolutionize anti-infective therapy by enabling continuous, real-time dosing adjustments based on patient-specific data.
By the end of this session, participants will gain a comprehensive understanding of the evolving landscape of anti-infective therapy, equipped with the tools necessary to implement these advanced strategies to optimize therapeutic target attainment.
Goals/Objectives:
1. Understand the Role of Therapeutic Drug Monitoring (TDM) in individualizing dosing and improving patient outcomes by adjusting drug levels for optimal therapeutic response.
2. Explore Model-Informed Precision Dosing (MIPD) as a cutting-edge approach to predict individualized drug doses based on pharmacokinetic (PK) models and patient-specific data, ensuring better efficacy and safety.
3. Examine the Importance of Target Site Concentrations in achieving effective drug exposure at the site of infection, highlighting the need for enhanced PK models that incorporate tissue penetration data.
4. Discuss Alternative Sampling Techniques such as saliva and dried blood spots, offering less invasive and more frequent options for monitoring anti-infective drug concentrations.
5. Delve into the Potential of Improved PK Models and how they can provide more accurate dosing recommendations through population-based approaches and dynamic modeling.
6. Review the Future of Machine Learning and Real-Time Monitoring, which could revolutionize anti-infective therapy by enabling continuous, real-time dosing adjustments based on patient-specific data.
By the end of this session, participants will gain a comprehensive understanding of the evolving landscape of anti-infective therapy, equipped with the tools necessary to implement these advanced strategies to optimize therapeutic target attainment.
Biography
Birgit CP Koch is Hospital Pharmacist-Clinical Pharmacologist and Full Professor of Clinical Pharmacometrics, working at Erasmus MC in Rotterdam. She supervises the education program for residents in Clinical Pharmacology.
Nowadays, she is member of the executive board of EPASG, the PK/PD group of ESCMID, council member of IATDMCT, member the pharmacology committee of UEMS, the specialist registration committee for hospital pharmacists and clinical pharmacologists in the Netherlands, member of ISAP, ASCPT, EACPT, the SWAB committee, the medical ethical board, the editorial board of therapeutic drug monitoring, British Journal of Clinical Pharmacology and Clinical Pharmacokinetics. She is member of the alternative sampling and infections committees of IATDMCT and NWO VIDI member. She is chair of the Young Investigator Grant Committee and chair of the expert team Knowledge security of Erasmus MC.
She authored > 230 publications on PK/PD, TDM and toxicology and she is the PI of several studies on model-based dosing, TDM and PK in antibiotics and psychoactive drugs, with funding > 2000 K. Her research focuses on alternative matrices, pharmacokinetics and pharmacodynamics of drugs in special populations and toxicology during pregnancy. At the moment, she supervises 21 PhD students (and 9 finished).
Dr Vikram Gota
Advanced Centre For Treatment, Research and Education in Cancer, Tata Memorial Centre, Mumbai
A randomized controlled trial of therapeutic monitoring-based dosing strategy versus standard dosing strategy of sunitinib in metastatic renal cell carcinoma
Abstract
Background:
Sunitinib, a multi-targeted tyrosine kinase inhibitor, is a standard first-line treatment for metastatic renal cell carcinoma (mRCC). We evaluated whether TDM-guided dosing of sunitinib improves treatment outcomes compared to conventional dosing in mRCC patients.
Methods:
This randomized, controlled trial enrolled patients with mRCC and randomized them in a 1:1 ratio to receive sunitinib (50 mg/day) either with TDM-guided dose optimization or conventional dose adjustments based on observed toxicity. In both arms, total trough levels (TTL) of sunitinib were measured between days 10–14 of cycle 1. In the TDM Arm, suitable dose adjustments were made, where necessary, to maintain TTL within the therapeutic range of 60–100 ng/mL. In the Standard Arm dose modifications were initiated only in case of intolerable side effects as per standard institutional practice. The primary endpoint was progression-free survival (PFS), while the key secondary endpoint was the incidence of grade ≥3 adverse events.
Results:
A total of 125 patients were enrolled, with 64 and 61 patients randomized to the Standard and TDM arms, respectively. TTL in cycle 1 were comparable between the arms (142 ng/mL vs. 145 ng/mL), but by cycle 4, median TTL of sunitinib decreased to 84 ng/mL in the TDM arm, reflecting dose adjustments, as against 124 ng/mL in the Standard Arm. The median PFS was 14.9 vs 14.7 months in the Standard arm and TDM arm (HR = 1.0, 95% CI: 0.669–1.493) respectively. Notably, grade ≥3 adverse events were markedly lower in the TDM arm (16.6%) compared to Standard Arm (49.2%).
Conclusion:
TDM did not significantly impact PFS. However, it markedly reduced the incidence of grade ≥3 adverse events, supporting its role in personalized dosing of sunitinib.
Sunitinib, a multi-targeted tyrosine kinase inhibitor, is a standard first-line treatment for metastatic renal cell carcinoma (mRCC). We evaluated whether TDM-guided dosing of sunitinib improves treatment outcomes compared to conventional dosing in mRCC patients.
Methods:
This randomized, controlled trial enrolled patients with mRCC and randomized them in a 1:1 ratio to receive sunitinib (50 mg/day) either with TDM-guided dose optimization or conventional dose adjustments based on observed toxicity. In both arms, total trough levels (TTL) of sunitinib were measured between days 10–14 of cycle 1. In the TDM Arm, suitable dose adjustments were made, where necessary, to maintain TTL within the therapeutic range of 60–100 ng/mL. In the Standard Arm dose modifications were initiated only in case of intolerable side effects as per standard institutional practice. The primary endpoint was progression-free survival (PFS), while the key secondary endpoint was the incidence of grade ≥3 adverse events.
Results:
A total of 125 patients were enrolled, with 64 and 61 patients randomized to the Standard and TDM arms, respectively. TTL in cycle 1 were comparable between the arms (142 ng/mL vs. 145 ng/mL), but by cycle 4, median TTL of sunitinib decreased to 84 ng/mL in the TDM arm, reflecting dose adjustments, as against 124 ng/mL in the Standard Arm. The median PFS was 14.9 vs 14.7 months in the Standard arm and TDM arm (HR = 1.0, 95% CI: 0.669–1.493) respectively. Notably, grade ≥3 adverse events were markedly lower in the TDM arm (16.6%) compared to Standard Arm (49.2%).
Conclusion:
TDM did not significantly impact PFS. However, it markedly reduced the incidence of grade ≥3 adverse events, supporting its role in personalized dosing of sunitinib.
Biography
Dr. Vikram Gota completed his MD in pharmacology from Christian Medical College, Vellore, following which he briefly worked as a Clinical Investigator in BA/BE studies. Thereafter, he joined the INDOOxford (INDOX) Cancer Trials Network at Tata Memorial Centre, Mumbai, where he received training in the design and conduct of phase I clinical trials. During this time, he also obtained the post graduate diploma in clinical trials from the London School of Hygiene and Tropical Medicine, University of London.
He is presently the officer-in-charge of the department of clinical pharmacology at the Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre. His research
interests include early clinical development and pharmacokinetics driven optimization of drugs used in cancer, including the development of pediatric-friendly formulations for childhood cancers. He is currently the Chair of the TDM in Oncology sub-committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT). He is involved with the geriatric clinic at TMH since 2019 focusing on rational therapeutics, potentially inappropriate medications and drug-drug interactions, among other things. He has worked as an investigator in several phase I clinical trials including first-in-human studies of investigational new drugs.
Session chair
Sophie Stocker
The University Of Sydney
