Conferences

25th North American ISSX Meeting Program

September 21-24, 2025
Chicago, IL

WuXi AppTec DMPK is proud to be exhibiting at the International Society for the Study Xenobiotics Meeting on September 21-24, 2025.

About The International ISSX Meeting

The ISSX meeting provides an exceptional opportunity to learn, network, and exchange ideas with researchers from around the world. Interact with a broad representation of international researchers and other scientists who are gaining a deeper understanding of drug metabolism and pharmacokinetics.

Presentation: To be updated soon

Exhibit Booth: To be updated soon

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Our posters

Other Resources

Our posters
Other Resources

- Desorption Strategies in Peptide Formulation Preparation: Insights from In Vitro Adsorption (Non-Specific Binding) Assessment Experiments
  
  A notable challenge in the formulation process is the observed discrepancy between the actual and nominated concentrations of test articles during preparation. The cause of this discrepancy is complex to identify, and it could stem from non-specific binding or adsorption of peptides onto various surfaces, such as filter membranes, glass containers, and plastic syringes. Other factors, including peptide stability issues, may also contribute to this problem.
- Individual Variability and Control of Gastric Acid pH in Fasting Cynomolgus Monkeys: Implications for Oral Drug Bioavailability Assessment
  
  This poster aims to systematically evaluate: The baseline variability of gastric pH in fasting cynomolgus monkeys; The efficacy of pharmacological interventions (pentagastrin and histamine) compared to direct acidification with hydrochloric acid (HCl) in standardizing gastric pH levels.
- Cremophor-Induced Immunogenicity in Beagle Dogs: Mechanistic Insights and Mitigation Strategies for Animal Injectable Formulations
  
  This study aims to systematically assess the safety profile of Cremophor-based excipients across different administration routes, thereby clarifying their risks in canine preclinical research and providing scientific evidence for new drug development.
- Nervous System Drug Nervous System Drug Delivery Techniques in Large Animals (Non-Rodents): Enhancing DMPK Research for Oligonucleotide DrugsDelivery Techniques in Large Animals (Non-Rodents): Enhancing DMPK Research for Oligonucleotide Drugs
  
  The intrathecal administration technique provides an effective delivery route for oligonucleotide drugs, overcoming of biological barriers and enhancing therapeutic efficacy, particularly in the treatment of central nervous system (CNS) diseases. In non-human primates, conventional intrathecal (IT) administration is typically performed via lumbar puncture, which suffers from a low success rate and inconsistent data. This inconsistency poses challenges for the development of new CNS drugs. In contrast, utilizing a lumbar catheter allows for a 100% success rate in drug administration as well as the potential for multiple repeated doses.
- Propylene Glycol Dose-Dependent Hemolysis in Intravenous Formulations: Thresholds and Mitigation Strategies in Beagle Dogs
  
  This poster investigates the hemolytic risks associated with PG dosing thresholds, co-solvent interactions, and strategies for mitigating hemolysis in beagle dogs.
- Fast Biomimetic High-Performance Liquid Chromatography Method for Evaluating Human Plasma Protein Binding
  
  This study developed a biomimetic high-performance liquid chromatography (HPLC) method to evaluate human plasma protein binding. This method employs a stationary phase containing human serum albumin (HSA) to mimic the biological environment of drug-protein binding. The chromatographic retention behavior of compounds on the biomimetic stationary phase reveals the affinity of compounds to albumin. This innovative approach overcomes the limitations of conventional techniques, offering a rapid and high-throughput strategy for assessing plasma protein binding of small molecules and peptides, which holds significant implications for efficacy and safety evaluations in drug discovery.
- Measurement of Phosphoinositide (PIP) Metabolism via Derivatization-Based Liquid Chromatography-Tandem Mass Spectrometry
  
  The parent ions and the characteristic fragment ions (glycerol backbone with fatty acyl chains) were utilized to distinguish PIP species with distinct fatty acyl chains or identical chains but varying phosphorylation states. Combined with chiral chromatography columns, PIPs sharing the same fatty acyl composition but differing in phosphorylation positions (e.g., PI(3,4)P2 vs. PI(3,5)P2) were effectively separated. This methodology enabled the successful identification of more than 60 PIP species in HeLa cells, demonstrating exceptional selectivity and sensitivity.
- The Strategy for UGT Enzyme Phenotyping
  
  In our experimental system, Nilotinib and Regorafenib, two UGT1A1 inhibitors recommended by ICH M12, were found to have off-target effects on UGT1A3 and 1A9, respectively, with off-target inhibition rates exceeding 60%. As a result, we have also verified the specificity of some of the inhibitors for UGT1A1, 1A3, 1A4, 1A9, 2B7, and 2B10 to support further research.
- Is the Direct or Indirect Method the Ideal One for Evaluation of Blood to Plasma Ratio?
  
  In vitro blood to plasma ratio (BPR) assays are important for understanding drug distribution into red blood cells (RBCs), thus informing a rational choice of appropriate biological fluid for pharmacokinetic analysis. Two methods, namely the direct method and the indirect method, are routinely performed in the industry. In the direct method, analyte concentrations in blood and plasma separated from blood are analyzed, while in the indirect method, analyte concentrations in plasma separated from blood, as well as an incubated plasma, are determined.
- Substrate and System-Dependent Activation of CYP2B6
  
  To ensure the activation of CYP2B6, different substrates and assay systems were applied in the study. In general, human liver microsomes (HLM) or recombinant human CYP enzymes were employed as enzyme sources. Bupropion hydroxylation and efavirenz hydroxylation, the marker reactions recommended by the ICH M12, were both used to evaluate the inhibition towards CYP2B6.
- Establishment of a Novel Funnel Model for Evaluating Blood-Brain Barrier Penetration in Vitro
  
  The Blood-Brain Barrier (BBB) Parallel Artificial Membrane Permeability Assay (PAMPA) model is frequently employed to predict passive BBB penetration in the early stages of Central Nervous System (CNS) drug development, and MDR1-MDCK I cell from the National Institutes of Health (NIH) is mainly used to exclude P-glycoprotein (P-gp, MDR1) substrates for CNS drug development . The two models have traditionally been applied independently. In this study, we combined both models to create a novel funnel model for the precise evaluation of BBB penetration in the early stages of CNS drug development.
- Application of Lecithin (PL90) and Poloxamer 188 in Permeability and P-GP/BCRP Mediated Drug Interaction Studies in Caco-2 Cells
  
  Highly lipophilic compounds typically exhibit poor aqueous solubility and high non-specific binding. These properties can make conventional in vitro permeability and P-gp/BCRP-mediated drug interaction studies infeasible at intended concentrations. Additionally, high non-specific binding may compromise experimental accuracy, potentially leading to the premature discontinuation of promising candidates.
- In Vitro Metabolic Stability Evaluation of Peptides
  
  Peptides are rapidly degraded by endogenous proteases in the bloodstream, stomach, intestine, liver, and kidney, hindering their entry into systemic circulation after oral administration. This study evaluated peptide metabolic stability across gastrointestinal, hepatic, renal, and circulatory systems to identify optimal in vitro models for guiding structural optimization.
- Pharmacokinetic Comparison of Pemetrexed Administered via Lumbar Intrathecal vs. Cisterna Magna Intubation in Sprague-Dawley Rats
  
  In the study of central nervous system (CNS) diseases, commonly employed methods of invasive drug administration in rats include lumbar and/or cisterna magna puncture and intubation.To further evaluate how these delivery routes affect PK profiles, we conducted a study comparing the PK profiles of Pemetrexed (MW: 427 g/mol) administered via lumbar intrathecal intubation versus cisterna magna intubation in Sprague-Dawley (SD) rats.
- Advancements in Exposed Polar Surface Area (EPSA) for Predicting Permeability in Early Drug Discovery
  
  This poster discusses the development of EPSA, reviews its applications as a predictive tool for passive membrane permeability, and highlights its significance in designing drugs with high oral bioavailability. We further optimized the chromatographic conditions (reducing single-needle detection time to 6.5 minutes) to measure EPSA, present data for a range of bRo5 and Ro5 compounds, and offer alternative high-throughput and high-quality detection methods for drug screening in the drug discovery stage.
- Novel Rat Intrathecal Catheterization Model for Direct Antisense Oligonucleotide (ASO) Drug Delivery to the Central Nervous System
  
  The methodology employs a guidewire-assisted catheter implantation through the cauda equina space (L5-L6 intervertebral region), achieving a total incision length of <5 mm to substantially reduce physiological stress caused by surgical procedures. Procedural efficiency is evidenced by an operation time of < 15 minutes per rat, a catheterization success rate > 95%, and a 100% postoperative survival rate. Importantly, this technique circumvents the neurological injury risks associated with traditional lumbar puncture while enabling persistent repeated dosing （more than 4 weeks）.
- Radiolabeling Synthesis and ADME Profiling of GLP-1 Analogs: Strategies and Preclinical Insights
  
  Glucagon-like peptide-1(GLP-1) mono-, dual-, and triple-receptor agonists, a class of engineered analogs derived from sequence modifications, exert pharmacological effects through activation of GLP-1 receptor or co-activation of receptors for Glucose-dependent insulinotropic polypeptide (GIP), and Glucagon (GCG). These analogs are primarily approved or in development for the management of type 2 diabetes and obesity. Current marketed GLP-1 analogs predominantly incorporate fatty acid chain modifications to enhance pharmacokinetic properties. For such lipid chain modified analogs, comprehensive absorption, distribution, metabolism, and excretion (ADME) studies are essential to elucidate their in vivo behavior.
- Probing Drug and Metabolite Covalent Binding with a Non-Radiolabeled Method: Osimertinib as an Example
  
  In this study, a novel LC-MS approach using targeted Precursor Ion Scan to identify protein-conjugated drug-related compounds was developed and optimized. After organic solvent extraction, the resulting residue of the incubated sample undergoes proteolytic digestion. We utilize non-targeted scanning for multiple fragment ions of the parent compound to identify products where the parent compound or its metabolites are covalently bound to amino acids or peptides. Using osimertinib as a model compound, we first conducted a conventional MetID study with the supernatant, followed by a MetID analysis of the residue after extraction. We investigated multiple matrices, including plasma and human serum albumin (HSA).
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