What are pharmacokinetic and toxicology studies, and what is their importance in drug discovery?
Understanding what a drug does in the body is paramount to developing safe and effective therapies. Pharmacokinetics (PK), pharmacodynamics (PD), and toxicokinetics (TK) are critical for this understanding. Pharmacokinetics describes what happens to a drug as it is absorbed, distributed, metabolized, and excreted (ADME), while pharmacodynamics examines the drug’s action on the body and mechanism of action. Together, they determine dose-exposure-response relationships and provide the basis for decision-making in drug development. For example, PK studies during clinical trials provide data on the duration and concentration of drug retention in systemic circulation. On the other hand, PD evaluates whether such concentrations result in the intended therapeutic effects.
PK/PD combined analysis allows researchers to evaluate efficacy, safety, and dose optimization more precisely. Early pharmacokinetic screening to establish interspecies and interindividual variability is necessary to estimate human response. Toxicokinetic testing facilitates safety evaluations by establishing a relationship between drug exposure and resulting toxicity. Cell-based assays are part of these studies, which are of enormous utility in early screening for modeling biological responses, predicting toxicities, and establishing the mechanism of action before animal or human trials. In addition, PK ADA assessment is needed for biologics to specify whether anti-drug antibodies affect drug exposure or response. PK, PD, TK, and Cell-based Assay data collectively constitute the scientific backbone of early drug development, steering the most promising drug candidates safely and efficiently toward clinical success.
ADMET (Absorption, Distribution, Metabolism, Elimination, Toxicity) tests are essential to drug discovery and development and offer important information regarding the toxicology and pharmacokinetics of future drugs. Usually performed under DMPK (Drug Metabolism and Pharmacokinetics) programs, these tests establish the amount of drug absorbed, its location within the body, how it will be metabolized and eliminated, and if it will be toxic. Researchers conduct these assessments in DMPK (Drug Metabolism and Pharmacokinetics) programs. As nearly 50% of drug leads are eliminated based on poor efficacy and as much as 40% based on toxicity, the utilization of ADMET screenings early during drug development is imperative today.
Laboratory bioanalytical services and experimental models both play equally key roles in yielding good-quality ADMET data. In vitro models, such as hepatocytes and liver microsomes, are extensively used to analyze metabolic enzymes, for example, UGT and CYP450. Cell-based assays, such as MDCK and CACO-2 models, assess the intestinal membrane permeability of drugs. Simultaneously, in vivo rodent and non-human primate pharmacokinetic models provide pertinent information on drug half-life, clearance, exposure, and bioavailability. They utilize bioanalytical laboratories to maintain tight GLP guidelines for data integrity and regulatory compliance.
The FDA and regulatory agencies have provided far-reaching guidance on drug metabolism, safety testing, and good laboratory practices to support these operations. Electronic solutions, such as Thermo Fisher’s Platform for Science™, have also been created to make ADME/Tox workflows easier, allowing laboratories to handle protocols, reagents, assay data, and results. The interaction between robust bioanalytical labs and carefully designed ADMET studies is essential to advance lead drug candidates through preclinical and clinical development and successful regulatory approval.
Must Read: Common Challenges in Large Molecule Bioanalysis and How to Overcome Them
How are bioanalytical labs crucial in conducting pharmacokinetic and toxicology studies?
Bioanalytical labs are indispensable to pharmacokinetic (PK) and toxicology studies during drug development. Bioanalysis labs generate precise information on drug concentrations, bioavailability, metabolism, elimination, guiding dose selection, dosing regimen, and therapeutic safety margins. Bioanalytical laboratory services in PK studies measure a drug’s absorption, distribution, metabolism, and excretion (ADME), which constitute the foundation for modeling drug action in the body and establishing dose-exposure-response relationships.
In drug exposure toxicology studies, bioanalytical laboratories quantify the drug through a set of doses to evaluate potential toxic effects and establish safety levels. This type of information is essential in preclinical development, wherein no-observed-adverse-effect levels (NOAELs) and human equivalent dose (HED) calculations are informed by toxicokinetic data. Each assay in a bioanalytical laboratory must comply with regulatory requirements and is typically run under Good Laboratory Practice (GLP) conditions to ensure the integrity and quality of data.
Laboratories commonly use assays such as LC-MS/MS, ELISA, and cell-based assays to measure drugs, metabolites, or biomarkers in various biological matrices. Such laboratories also design and validate assays for immunogenicity detection, pharmacodynamic (PD) marker measurement, and drug interaction quantitation. Complexity in biological matrices and species differences demand extremely high analytical precision and method observational ruggedness, which bioanalytical laboratories are firmly placed to deliver.
Lastly, Bioanalytical Lab services are essential to bridge experimental findings to actionable data that guides regulatory submissions, clinical trial design, and therapeutic safety. Their technical capabilities and regulatory expertise help drug developers to move drug candidates through all stages of development.
Conclusion:
Bioanalytical laboratories spearhead pharmacokinetic and toxicology research, providing the key information to ascertain a drug’s efficacy and safety in organisms. Bioanalytical laboratories fill the nexus between initial method development and post-marketing surveillance, providing precise quantification of drug concentration, metabolites, and biomarkers. Their work underpins key decisions related to dosing, efficacy, and toxicity, helping to guide regulatory submissions and clinical trial design. By delivering scientifically robust and compliant data, bioanalytical labs enable pharmaceutical developers to bring safe and effective therapies to patients confidently.
