Pharmacokinetics (PK) Study: Drug Concentration vs. Time in the Body

A pharmacokinetic study provides the basis for determining drug exposures in the body over time. PK parameters are used in the evaluation of the absorption, distribution, metabolism, and excretion (ADME) processes of drugs.

Absorption

Absorption, the first topic of PK studies, is the initial process by which drugs enter the blood circulation following dosing. Drug substances in PK lab testing can be administered to the body through several routes such as oral, nasal, dermal, or parenteral. Absorption at the gastrointestinal tract, one of the most common drug absorption sites, is affected by several factors including physicochemical parameters of the drug, gastrointestinal motility, drug concentration, and ionization state at the site of absorption.

Distribution

Distribution is a reversible drug transfer within the body from one location to another. The distribution of a drug can be influenced by several factors such as lipid-solubility, concentration in plasma and various tissues, and protein binding of drugs in plasma and tissues. PK studies assess whether compounds can distribute throughout the body readily or are confined to the bloodstream once absorbed.

Metabolism

Metabolism, an essential topic of PK analysis, is the process by which a drug is converted to another chemical entity (metabolite). Metabolism happens primarily in the liver and is classified into two broad categories: Oxidative metabolism includes hydrolysis, oxidation, and reduction reactions driven mainly by the cytochrome P450s, monooxygenase systems, and alcohol dehydrogenases. The typical chemical reactions involved in oxidative metabolism include aromatic hydroxylation, aliphatic hydroxylation, oxidative N dealkylation, oxidative O-dealkylation, S-oxidation, reduction, methylation, and hydrolysis. Most often, these reactions increase compound polarity to make a drug more soluble, facilitating elimination through the kidneys. In conjugative metabolism, conjugation occurs by glucuronidation, sulfation, amino acid conjugation, acetylation, or glutathione conjugation to aid elimination. Enzymes involved in conjugation include UDP glucoronyl transferases, aryl sulfatases, N-acetyl transferases, and glutathione S-transferases. Conjugation can serve to inactivate a compound or make it more readily eliminated by urinary or biliary excretion. Several factors influence a drug’s rate of metabolism, including the route of administration, dose, genetics, disease state, and metabolic activity.

Excretion

Eliminating the drug and other toxic substances from the body, the last topic of the PK study, is known as the process of excretion. Most drugs in the body are eliminated through the urine. Excretion also depends on the solubility of the drug in water. More soluble drugs are excreted faster in the urine. If the excretion is incomplete, the accumulation of compounds in the body can lead to adverse events. Pharmacokinetics study testing should incorporate sufficient sampling times during compound elimination for appropriate assessments of parameters such as elimination half-life and clearance.

PK Analysis: From Drug Discovery and Preclinical to Clinical Phases

PK analysis is performed throughout the drug research and development process, starting from early discovery to the last Phase of drug development. The primary purpose of preclinical pharmacokinetic studies is to evaluate the characteristics of potential drugs to predict exposures and determine dose levels and frequencies for testing new chemical entities in preclinical disease efficacy models. PK studies in multiple species can be used to predict human pharmacokinetics and estimate the dose required for clinical efficacy and potential manufacturing costs for the intended drug product after achieving therapeutic proof-of-concept and honing structure-activity-relationships (SAR) to determine lead molecules. Pharmacokinetic (PK) Assays during the preclinical phase help determine bioavailability, the volume of distribution, half-life, and clearance. These PK studies help evaluate if the drug has adequate success potential or needs to be modified to improve its pharmacokinetic parameters. Pharmacokinetic (PK) study results from the preclinical stage help design IND enabling Tox studies in animals, and drugs can be advanced farther into clinical development based on these preclinical results. PK bioanalysis meeting the requirements for first in human (FIH) dosing initially undergo single ascending dose (SAD) clinical trials to assess the safety and clinical pharmacokinetics, followed by later multiple ascending dose (MAD) clinical trials to assess steady-state exposures and to correlate with drug pharmacology.

PK Assay and PK Analysis Services by NorthEast BioLab

PK Assay and PK Analysis Services by NorthEast BioLab

We offer a wide range of Pharmacokinetic (PK) Assays beginning from the early discovery phase when a potential drug compound is administered to rodents for understanding ADME properties. Once a compound is found suitable for further development, we also provide Pharmacokinetic (PK) testing services for dose range finding studies followed by IND enabling Toxicology (Tox) studies in rodent and non-rodent animals. PK studies in animals are critical for safely advancing the drug into clinical development. We provide pharmacokinetics services during clinical trials by developing and validating bioanalytical methods in the human biological matrices post the FDA approval of your IND application.

Once your PK bioanalysis is completed, we can complete your Pharmacokinetics (PK) study by calculating relevant parameters for your compound. Additionally, we are glad to assist you with protocol and study design, study execution, and interpretation of your PK data, and/or provide guidance on compound selection, dose levels, collection intervals for preclinical efficacy testing. We maintain fully validated Phoenix WinNonlin software at our facility for non-compartmental analyses (NCA) and PK modeling. Our team can generate formally audited bioanalytical reports for all your regulated studies from early discovery through clinical development.

Introduction to Pharmacokinetics

Pharmacokinetics (PK) is the analysis and description of the disposition of a drug in the body, encompassing development of the mathematical description of all dispositional processes in the body, defined as ADME – absorption, distribution, metabolism, and elimination…

Accurate Pharmacokinetics (PK) Study to Assess your Drug's Proper Exposure and Therapeutic Potential

Pharmacokinetics studies for ADME and toxicokinetic analysis demand both in-depth expertise and nimble execution. NorthEast BioLab is the right partner to assist you in bringing new, effective drugs to the market given the critical and detail-orientated nature of these PK studies in pharmaceutical drug development.

Our team of veteran scientists can help discern your top drug compound based on our 15+ years of experience in method development, validation, transfer for PK bioanalysis and related assay. Together, we can develop robust bioanalytical methods to support your PK studies for the analysis of drugs and metabolites in biological fluids followed by the calculation of PK parameters by non-compartmental analysis (NCA). We promise a high quality and take full responsibility for all your projects, including compliance with various regulations mandated by authorities and agencies such as FDA and ICH.

Related FAQs

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