We are offering pharmacokinetic (PK) studies using your prodrug or metabolites can be made safer by using FDA-audited PK and ADA assay services.

We are providing Clinical pharmacokinetics services with industry-leading turnaround fully validated GLP PK bioanalysis on LC-MS/MS, ELISA, MSD, or qPCR.

What is Pharmacokinetic (PK) Study?

For figuring out how long-term drug exposures last in the body, pharmacokinetic studies serve as the foundation. When assessing how well a drug is absorbed, distributed, metabolized, and excreted (ADME), PK parameters are utilized.

Absorption

The first step in the process by which drugs enter the bloodstream after dosing is called absorption, and it is the focus of PK studies. Several routes, including oral, nasal, dermal, and parenteral, can be used to administer drug substances to the body during PK lab testing. One of the most frequent drug absorption sites, the gastrointestinal tract, is affected by a number of variables, including drug concentration, gastrointestinal motility, and the ionization state of the absorption site.

Distribution

The term “distribution” refers to the reversible movement of drugs from one part of the body to another. The concentration of a drug in plasma and different tissues, its solubility in lipids, its binding to proteins in plasma and tissues, and other factors can all affect how a drug is distributed. PK studies determine whether substances are confined to the bloodstream after absorption or can easily distribute throughout the body.

Metabolism

The process by which a drug is changed into another chemical substance (metabolite), metabolism is a crucial component of PK analysis. Mainly taking place in the liver, metabolism can be divided into two categories: The cytochrome P450s, monooxygenase systems, and alcohol dehydrogenases are primarily responsible for the hydrolysis, oxidation, and reduction reactions that make up oxidative metabolism. A few of the typical chemical processes in oxidative metabolism are aromatic hydroxylation, aliphatic hydroxylation, oxidative N dealkylation, oxidative O-dealkylation, S-oxidation, reduction, methylation, and hydrolysis. The majority of the time, these reactions increase compound polarity to make a drug more soluble, facilitating kidney elimination. To aid in elimination, conjugation takes place in conjugative metabolism through the processes of glucuronidation, sulfation, amino acid conjugation, acetylation, or glutathione conjugation. UDP glucoronyl transferases, aryl sulfatases, N-acetyl transferases, and glutathione S-transferases are some of the enzymes involved in conjugation. A compound may become inactive through conjugation, or it may become more excretable through the urinary or biliary systems. The route of administration, dose, genetics, disease state, and metabolic activity are some of the variables that affect a drug’s rate of metabolism.

Excretion

The final component of the PK study is excretion, which is the process of removing the drug and other harmful substances from the body. The urine is the primary method of drug elimination from the body. The drug’s solubility in water has an impact on excretion as well. Urine excretion of soluble drugs is accelerated. When compounds build up in the body due to insufficient excretion, negative effects may result. For accurate assessments of parameters like clearance and elimination half-life, pharmacokinetics study testing should include enough sampling times during compound elimination.

When is PK analysis performed?

PK analysis is carried out at every stage of the drug research and development process, from early discovery to the final Phase. Preclinical pharmacokinetic studies’ main goal is to assess potential drugs’ properties in order to forecast exposures and choose the appropriate doses and testing schedules for novel chemical entities in these models of preclinical disease efficacy. After achieving therapeutic proof-of-concept and refining structure-activity-relationships (SAR) to identify lead molecules, PK studies in various species can be used to predict human pharmacokinetics, estimate the dose necessary for clinical efficacy, and potential manufacturing costs for the intended drug product.

Bioavailability, the volume of distribution, half-life, and clearance are all determined by pharmacokinetic (PK) assays during the preclinical phase. These PK studies aid in determining whether the drug has a sufficient chance of success or whether it requires revision to enhance its pharmacokinetic parameters. Drugs can be developed further in the clinical stage based on the results of preclinical pharmacokinetic (PK) studies that help design IND enabling Tox studies in animals. First, single ascending dose (SAD) clinical trials are used to evaluate the safety and clinical pharmacokinetics of PK bioanalysis that satisfies the requirements for first in human (FIH) dosing. Later, multiple ascending dose (MAD) clinical trials are used to evaluate steady-state exposures and to correlate with drug pharmacology.

discover more about pharmacokinetics The study of a drug’s disposition in the body is called pharmacokinetics (PK), and it includes the mathematical formulation of all dispositional processes in the body, which are absorption, distribution, metabolism, and elimination (ADME)….

We provide a variety of PK assay and PK analysis services.

We provide a wide range of pharmacokinetic (PK) assays, starting with those used in the early stages of drug discovery when rodents are given potential drug compounds to better understand their ADME properties. We also offer pharmacokinetic (PK) testing services for dose range finding studies after a compound is deemed suitable for further development, which is followed by IND-enabling toxicology (Tox) studies in rodent and non-rodent animals. In order to safely advance the drug into clinical development, PK studies in animals are essential. Following FDA approval of your IND application, we develop and validate bioanalytical methods in human biological matrices to provide pharmacokinetics services during clinical trials.

After your PK bioanalysis is finished, we can finish your PK study by computing the necessary parameters for your compound. Furthermore, we are happy to help you with protocol and study design, study execution, and interpretation of your PK data, as well as to offer suggestions on the choice of compound, dose levels, and collection intervals for preclinical efficacy testing. At our facility, we maintain fully validated Phoenix WinNonlin software for PK modeling and non-compartmental analyses (NCA). For each and every one of your regulated studies, from early discovery through clinical development, our team can produce officially audited bioanalytical reports.

What makes us your best choice for your pharmacokinetics (PK) study?

In-depth knowledge and quick execution are required for pharmacokinetics studies for ADME and toxicokinetic analysis. Given the critical and meticulous nature of these PK studies in pharmaceutical drug development, GCC is the ideal partner to help you bring new, efficient medications to market.

Based on our team’s 20+ years of experience in method development, validation, transfer for PK bioanalysis, and related assays, we can determine your top drug compound. Together, we can create reliable bioanalytical techniques to aid in the analysis of drugs and metabolites in biological fluids and the subsequent non-compartmental analysis (NCA) calculation of PK parameters. We guarantee top quality and assume full accountability for all of your projects, including adherence to the various rules required by authorities and organizations like the FDA and ICH.

By using our FDA-audited Pharmacokinetics (PK) Study Assay, Testing, and Sample Analysis Services, which we’ve been providing to top biotech and pharma companies since the early 2000s, you can immediately reduce the risk associated with your drug portfolio. We regularly carry out SAD MAD Pharmacokinetics (PK) Studies to ascertain how drugs behave in the body and to aid in crucial dosage and safety decisions. Our scientists use WinNonlin software and a fully validated assay to generate and model your GLP PK bioanalysis data. To begin working with us on your first PK Assay, speak with one of our scientists.

What does PK mean when it comes to clinical trials?

To investigate a drug’s absorption, distribution, metabolism, and excretion, we conduct PK studies in clinical trials. These studies are helpful in determining the safe and effective dose range for upcoming trials. In pharmacokinetic (PK) testing, the time course of a drug in the body is quantitatively analyzed. To investigate dosage proportionality and to correlate the PK effect changes with repeated dosage, PK testing in clinical trials frequently evaluates single ascending doses (SAD studies) and multiple ascending doses (MAD studies). Clinical trial SAD and MAD PK studies shed light on metabolic changes and the achievement of steady-state exposures during chronic therapies. Other clinical PK studies include those looking at drug penetration, drug-drug interaction (DDI) potential, and bioavailability and bioequivalence.

What are PK tests used for primarily?

We frequently carry out PK testing during the early stages of drug discovery to check whether new chemical entities (NCEs) have sufficient exposures for in vivo efficacy models in mice. We typically carry out in-vitro pharmacokinetic services to screen out substances with high metabolic rates or weak absorption potential even before dosing in the animals. To prepare for toxicology and toxicokinetics studies, pharmacokinetic testing in additional species is typically carried out in one rodent species and one non-rodent species during preclinical development. Allometry or other scaling models are additional PK services that use preclinical data to predict clinical PK prior to clinical trials. To ensure safety and establish the clinical PK parameters while ramping up to therapeutic doses, early clinical PK studies are frequently carried out at low-effective doses with slow dose escalation.

How are pharmacokinetic studies conducted?

Even though it varies depending on the chemical structures of the tested compounds and the intended therapeutic targets, pharmacokinetic (PK) study design adheres to some fundamental general principles. We firstly dissolve the test substance in a suitable dosing vehicle. After administering the vehicle dose to the test species, blood samples are taken over a predetermined time period to be analyzed for drug concentrations. The blood draw time vs. concentration curves are then plotted, and PK parameters like the area under the curve, maximum concentration, clearance, distribution volume, elimination half-life, etc. are calculated. In order to achieve our objective of demonstrating compound efficacy and safety with the end goal of reaching the clinic and market, we choose the species and strains for pharmacokinetics studies in animals.

What role does pharmacokinetics analysis play in the creation of new medications?

An examination of a test compound’s pharmacokinetics provides precise details about its course within the body. The relationship between the dosage schedule and the body’s exposure to the medication is the main topic of pharmacokinetics research. Typically, non-compartmental analysis is used to produce PK data. Area under the curve (AUC), maximum exposure (Cmax), clearance (CL or CL/F), distribution volume (Vd or Vd/F), elimination half-life (t12), and others are non-compartmental PK parameters. These parameters offer vital details about a drug’s rates of absorption and elimination, as well as its potential to reach tissues all over the body. Pharmacokinetics from a variety of species can be used to forecast dosing levels and regimens for animal disease models’ efficacy as well as the doses necessary for preclinical toxicology studies.

What are the study’s four main pharmacokinetic components?

Pharmacokinetic assays offer a numerical account of how the body reacts to a drug. The pharmacokinetics process is made up of four main parts: absorption, distribution, metabolism, and excretion, or ADME. The process of getting a drug from the site of delivery into the systemic circulation is called absorption. For instance, substances taken orally must be soluble in the gut environment, pass through the gastrointestinal tract, the liver, and the portal vein (known as the first pass) before entering the central nervous system. The drug’s ability to enter and exit central circulation to reach tissues and organs all over the body is referred to as distribution.

How do pharmacokinetics and pharmacodynamics differ from one another?

The effects of a drug on the body are described by pharmacodynamics, and the effects of a drug on the body are described by pharmacokinetics. In-vivo pharmacology includes both pharmacokinetics (PK) and pharmacodynamics (PD). Pharmacokinetics measures systemic exposure over time to assess drug absorption, distribution, metabolism, and excretion. The field of pharmacodynamics investigates the connection between drug concentration at the receptor, the site of action, and the pharmacological response that is perceived. Drug exposure is described by PK, and drug effects are described by PD. The relationship between the drug’s in-vivo exposure and effectiveness is revealed by PK PD analysis. Predictions of initial dosage levels and regimens for safety and efficacy in the clinic are frequently helpful thanks to PK PD studies conducted in a variety of species during drug discovery and development.

What exactly are PK (pharmacokinetic) parameters?

Drug discovery, development, and clinical testing depend heavily on in-vivo PK drug assessments. Depending on the study design, non-compartmental pharmacokinetic (PK) drug parameters may include the volume of distribution (Vd) and total plasma clearance (CL) after intravenous doses, time to maximum concentration (Tmax), maximum observed concentration (Cmax), area under the plasma concentration versus time curve (AUC), elimination half-life (t1/2) for all dose routes, and bioavailability (F%) when extravascular and intravenous routes have been tested. In accordance with your needs, the skilled scientists at NorthEast BioLab can help you with all project phases, including study and protocol design, study monitoring, sample bioanalysis, pharmacokinetics parameter calculation using verified Phoenix WinNonlin software, and result interpretation.